Methods for treating erectile dysfunction with a cgmp-specific phosphodiesterase 5 inhibitor pharmaceutical composition

ABSTRACT

A method is provided for treating erectile dysfunction in a subject in need thereof by administering a cGMP-specific phosphodiesterase 5 (PDE 5 ) inhibitor pharmaceutical composition to a subject qualified for over-the-counter access to the PDE 5  inhibitor pharmaceutical composition. In some embodiments, the PDE 5  inhibitor pharmaceutical composition includes tadalafil or vardenafil.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. patent application Ser. No.16/440,811 filed Jun. 13, 2019, now U.S. Pat. No. 11,348,670, whichclaims priority to U.S. Provisional Patent Application Ser. No.62/685,230, filed Jun. 14, 2018, which are hereby incorporated byreference in their entireties.

TECHNICAL FIELD

The present disclosure relates generally to methods for treatingerectile dysfunction by administering an over-the-counter cGMP-specificphosphodiesterase 5 inhibitor pharmaceutical composition to a subject inneed thereof, who has been qualified for over-the-counter access to thecomposition.

BACKGROUND

The prevalence of erectile dysfunction is growing worldwide. Forexample, it was estimated that the number of global diagnoses oferectile dysfunction will approximately double from 152 million patientsin 1995 to 322 million patients by 2025. Ayta I A et al, BJU Int.84(1):50-6 (1999). Moreover, erectile dysfunction is vastlyundertreated. For instance, analysis of data from a population of 6.2million patients with a known diagnosis of erectile dysfunction, showedthat approximately 75% of these patients went untreated. Frederick L R,et al., J Sex Med. 11(10):2546-53 (2014).

Fortunately, erectile dysfunction can be managed, for example, using acGMP-specific phosphodiesterase 5 (PDE₅) inhibitors, which are wellestablished prescription pharmaceuticals used to treat erectiledysfunction. For instance, the efficacy of tadalafil, which was firstapproved in the U.S. for the treatment erectile dysfunction in 2011, hasbeen demonstrated in at least five double-blind, placebo-controlled,randomized studies (Rashid A., 2005, “The Efficacy and Safety of PDE5Inhibitors,” Clin Cornerstone, 7(1), p 47). However, access to PDE₅inhibitors is restricted by the requirement for a prescription.Unfortunately, long-term trends demonstrate many people avoidprescription medications, including PDE₅ inhibitors.

One approach to making PDE₅ inhibitors more accessible is to make themavailable without a prescription, e.g., over the counter (“OTC”). Thereare a variety of health benefits derived from switching a drug fromprescription to OTC including generating wider availably to therapies,providing a greater number of therapeutic approaches, providing directand rapid access to treatments, providing patients with an active rolein their own health care, and allowing patients to become self-reliantin preventing and relieving minor symptoms or conditions (World HealthOrganization, 2000, “Guidelines for the Regulatory Assessment ofMedicinal Products for use in Self-Medication,” Print). Given the largenumber of individuals with erectile dysfunction, providing access to OTCPDE₅ inhibitors could provide significant societal health benefits.

However, switching distribution of a pharmaceutical fromprescription-only to OTC creates a significant risk that the patientpopulation will be unable to appropriately self-select themselves forsafe use of the pharmaceutical use and then self-medicate using the drugin a responsible manner. The manifestations embodied within theseconcerns include incorrect self-diagnosis, incorrect drug-qualification,unrecognized drug-drug interactions (DDI), unanticipated adverse drugreactions and/or side-effects, improper dosing and/or administration,masking of a disease, addiction, inappropriate drug dependency,substance abuse, and patient delay in seeking necessary medicalattention. Ruiz et al., Current Drug Safety, 5(4):315 (2010).

Because PDE₅ inhibitors cause adverse effects in certain patients, thepopulation receiving the drug should be carefully selected andmonitored. In order to ensure the safety of OTC distribution of PDE₅inhibitors, prospective patients must effectively self-select themselvesfor the drug. Recent studies, however, found that many prospectivepatients do not pay consistent attention to guidelines printed on thepackaging of OTC drugs, to ensure safe and responsible use. PR NewswireAssociation, “Americans Should Pay More Attention to Over-the-Counter(OTC) medicine Labels According to New Survey,” Oct. 15 (2015) (citingMcNeil Consumer Healthcare research). According to these studies, 40% ofprospective patients consider the directions as just guidelines and 80%of patients do not re-read the label of an OTC medicine they have usedbefore. Even more troubling, only 58% of men surveyed found it veryimportant to pay attention to restrictions on an OTC label.

Currently, there are two regulatory pathways for legal marketing of anOTC drug in the United States. In the first pathway, marketing occurs incompliance with an OTC drug monograph, that sets regulatory standardsfor non-prescription drugs that are not covered by human drugapplications, e.g., a New Drug Application (NDA) or Abbreviated New DrugApplication (ANDA). An OTC monograph is created as a result of a threephase OTC drug review by the FDA. In phase I of the review, an advisoryreview panel determines whether ingredients in the proposed OTCcomposition could be generally recognized as safe and effective for usein self-treatment. In the second pathway, marketing occurs under theauthority of an approved product-specific new drug application (NDA), oran abbreviated new drug application (ANDA). In order to support anover-the-counter label for a drug for which regulatory approval is beingsought through an NDA, a consumer research study is required to assessthe consumer's ability to select and deselect themselves as appropriateusers of the drug, based on the proposed labeling for the drug. Oliver,A., Regulatory Rapporteur, 10(3):4-9 (2013), which is incorporated byreference herein.

However, attempts at switching distribution of drugs having potentiallyfar-reaching benefits for societal health, from prescription-only to anOTC model, have repeatedly failed, in large part due to concerns overinappropriate patient selection and medication. Possibly the bestdocumented cases relate to statins used to treat high cholesterol.

For instance, Merck has had at least three applications for sale of overthe counter lovastatin rejected by the FDA, in 2000, 2005, and 2007. In2005, their proposal to permit over the counter sales of lovastatin wasrejected by an expert advisory panel at the FDA in 2005. The panel wasconcerned by a marketing study performed to support the proposal inwhich approximately one third of 3316 customers who were offered thedrug over the counter decided they would purchase the drug. Afterreviewing the data, the panel concluded that 45% of the purchases wouldhave been inappropriate for a variety of reasons, including the age ofthe subject, the subject's lack of knowledge about their condition, andcontraindications associated with their condition. Dyer O., BMJ,330(7484):164 (2005). In 2007, the board again concluded that theability of consumers to appropriately self-select and to adequatelycomply with chronic MEVACOR® therapy without the intervention of aphysician had not been demonstrated. Division of Metabolic and EndocrineDrug Products, 2005, “NDA 21-213 Non-prescription MEVACOR® 20 mg JointAdvisory Committee Meeting.”

Similarly, Pfizer announced in 2011 its intention to switch LIPITOR®from prescription-only to OTC status. Sett OTC bulletin, 16 Nov. 2011,page 7. However, they abandoned their attempt in 2014 when a phase 3“actual use” trial, intended to simulate the OTC use of LIPITOR®(atorvastatin calcium) 10 mg, failed to meet its primary objectives onthe basis that patient compliance with the direction to check theirlow-density lipoprotein cholesterol (LDL-C) level and, after checkingtheir LDL-C level, take appropriate action based on their test resultswas unsatisfactory. Pfizer Inc., “Pfizer Reports Second-Quarter 2015Results,” (2015).

In fact, in the nearly two decades since Bristol-Myers Squibb and Merck& Co first failed in their attempts to switch PRAVACHOL® and lovastatin,respectively, to OTC, a statin has never been granted OTC status in theUnited States. This is despite that nearly ⅙th of the adult populationin the U.S. is eligible for cholesterol-lowering medications, under thecurrent guidelines, but are not taking anything.

The information disclosed in this Background section is only forenhancement of understanding of the general background of the inventionand should not be taken as an acknowledgment or any form of suggestionthat this information forms the prior art already known to a personskilled in the art.

SUMMARY

Given the above background, what is needed in the art are systems andmethods for qualifying a human subject for delivery of a cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical compositionover-the-counter for treating erectile dysfunction.

The present disclosure addresses the need in the art for systems andmethods configured for qualifying a human subject for over-the-counterdelivery of a cGMP-specific phosphodiesterase 5 (PDE₅) inhibitorpharmaceutical composition (e.g., tadalafil) for treating erectiledysfunction. In the present disclosure, systems and methods are providedfor over-the-counter delivery of a PDE₅ inhibitor pharmaceuticalcomposition to a subject. Survey results from the subject are runagainst a first plurality of filters. When a filter in the firstplurality is fired, the subject is deemed not qualified for delivery ofthe PDE₅ inhibitor pharmaceutical composition. The survey results arealso run against a second plurality of filters. When a respective filterin the second plurality is fired, the subject is provided with acorresponding warning. The method proceeds to a fulfillment process whenno filter in the first plurality is fired and the subject hasacknowledged each warning associated with each fired filter in thesecond plurality of filters. The fulfillment process stores thecomposition order, communicates a drug facts label for the PDE₅inhibitor pharmaceutical composition to the subject, and authorizes,upon subject confirmation that the label has been read, provision ofPDE₅ inhibitor pharmaceutical composition to the subject.

Accordingly, one aspect of the present disclosure provides a method forqualifying a subject for over-the-counter delivery of a PDE₅ inhibitorpharmaceutical composition in order to treat erectile dysfunction of thesubject. The method includes conducting a first survey of the subject inorder to obtain a variety of survey results. In some embodiments, thesurvey results indicate one or more of: a gender of the subject, an ageof the subject, an erectile dysfunction status of the subject, whetherthe subject is taking a nitrate or nitrite vasodilator composition,whether the subject is taking a guanylate cyclase stimulator medication,whether the subject is taking a PDE₅ inhibitor composition, whether thesubject has ever had a heart problem, a blood pressure status of thesubject, whether the subject has ever had a stroke, whether the subjecthas a liver problem, a kidney function status of the subject, whetherthe subject has retinitis pigmentosa, whether the subject has developedvision loss, whether the subject has ever had a stomach ulcer, whetherthe subject has a bleeding disorder, a genital status of the subject,whether the subject has ever experienced priapism, whether the subjecthas a blood cell disorder, and whether the subject is taking amedication that interacts (e.g., a pharmacokinetic interaction and/or apharmacodynamic interaction) with the PDE₅ inhibitor pharmaceuticalcomposition.

The method also includes running all or a portion of the survey resultsagainst a first plurality of filters of a first category class,corresponding to contraindications associated with the PDE₅ inhibitorpharmaceutical composition. When a respective filter in the firstplurality of filters is fired, the subject is deemed not qualified fordelivery of the PDE₅ inhibitor pharmaceutical composition, and themethod is then terminated accordingly without delivery of the PDE₅inhibitor pharmaceutical composition to the subject. In someembodiments, the first plurality of filters includes one or more of agender filter, an age filter, an erectile dysfunction filter, avasodilator filter, a guanylate cyclase stimulator filter, and a PDE₅inhibitor filter.

The method also includes running all or a portion of the survey resultsagainst a second plurality of filters of a second category class,corresponding to risk factors associated with the PDE₅ inhibitorpharmaceutical composition. When a respective filter in the secondplurality of filters is fired, the subject is provided with a warningcorresponding to the respective filter. In some embodiments, the secondplurality of filters includes one or more of a first heart problemfilter, a first blood pressure filter, a first stroke filter, a firstliver disease filter, a first kidney disease filter, a first retinitispigmentosa filter, a first stomach ulcer filter, a first bleedingproblem filter, a first genital abnormality filter, a first priapismfilter, a first blood cell disorder, and a first drug interactionfilter. However, unlike filters in the first plurality of filters,filters in the second plurality of filters do not automaticallyterminate the process without delivery of the PDE₅ inhibitorpharmaceutical composition to the subject.

The method continues by obtaining acknowledgment from the subject forthe warning issued to the subject by any filter in the second pluralityof filters.

The method continues by proceeding with a fulfillment process when nofilter in the first plurality of filters has been fired and the subjecthas acknowledged each warning associated with each filter in the secondplurality of filters that was fired.

In some embodiments, the fulfillment process includes storing anindication in a subject profile of an initial order for the PDE₅inhibitor pharmaceutical composition, communicating an over-the-counterdrug label for the PDE₅ inhibitor pharmaceutical composition, andauthorizing, upon confirmation from the subject that theover-the-counter drug label has been received and read, provision of thePDE₅ inhibitor pharmaceutical composition to the subject.

In some embodiments, the PDE₅ inhibitor pharmaceutical composition hasthe structure:

where,

R⁰ represents hydrogen, halogen or C₁₋₆ alkyl;

R¹ represents hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, haloC₁₋₆alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl-C₁₋₃ alkyl, arylC₁₋₃ alkyl orheteroarylC₁₋₃ alkyl;

R² represents an optionally substituted mono-cyclic aromatic ringselected from benzene, thiophene, furan and pyridine or an optionallysubstituted bicyclic ring

attached to the rest of the molecule via one of the benzene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which maybe saturated or partially or fully unsaturated and comprises carbonatoms and optionally one or two heteroatoms selected from oxygen,sulphur and nitrogen; and

R³ represents hydrogen or C1-3 alkyl, or R¹ and R³ together represent a3- or 4-membered alkyl or alkenyl chain,

or a pharmaceutically acceptable salt thereof.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes tadalafil or a pharmaceutically acceptable salt thereof. Insome embodiments, the PDE₅ inhibitor composition includes vardenafil.

In one aspect, the present disclosure provides a method for qualifying asubject (e.g., a subject who was previously qualified to receive aprovision of the PDE₅ inhibitor pharmaceutical composition) for are-order of the PDE₅ inhibitor pharmaceutical composition (e.g., whichis optionally performed in conjunction with a method for qualifying thesubject for a first order of the PDE₅ inhibitor pharmaceuticalcomposition). The method includes a re-fulfillment procedure thatincludes conducting a second survey of the subject in order to obtain asecond plurality of survey results. In some embodiments, the secondplurality of survey results indicate one or more of: an erectiledysfunction status of the subject, whether the subject has started totake a nitrate or nitrite vasodilator composition since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition, whetherthe subject has started to take a guanylate cyclase stimulatormedication since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, whether the subject has started to take aPDE₅ inhibitor composition since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, whether the subject hasdeveloped symptoms of heart problems during sexual intercourse sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, whether the subject has experienced priapism sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, whether the subject has developed hearing or vision losssince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, whether the subject has developed a symptomof heart problems since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, a blood pressure status of thesubject, whether the subject has had a stroke since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition, whether thesubject has developed a liver problem since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition, a kidneyfunction status of the subject, whether the subject has developedretinitis pigmentosa since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developeda stomach ulcer since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developeda bleeding disorder since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developedan abnormal genital shape since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, whether the subject hasdeveloped a blood cell disorder since receiving their last provision ofthe PDE₅ inhibitor pharmaceutical composition, and whether the subjecthas started taking a medication that interacts with the PDE₅ inhibitorpharmaceutical composition since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition.

The method also includes running all or a portion of the secondplurality of survey results against a third plurality of filters of thefirst category class, corresponding to contraindications associated withthe PDE₅ inhibitor pharmaceutical composition. When a respective filterin the third plurality of filters is fired, the subject is deemed notqualified for the PDE₅ inhibitor pharmaceutical composition and, there-fulfillment process is terminated without delivery of the PDE₅inhibitor pharmaceutical composition to the subject. In someembodiments, the third plurality of filters includes an erectiledysfunction filter, a vasodilator filter, a guanylate cyclase stimulatorfilter, a PDE₅ inhibitor filter, a sexual intercourse filter, a priapismfilter, and a sensory deterioration filter.

The method also includes running all or a portion of the secondplurality of survey results against a fourth plurality of filters of thesecond category class, corresponding to risk factors associated with thePDE₅ inhibitor pharmaceutical composition. When a respective filter inthe fourth plurality of filters is fired the subject is provided with awarning corresponding to the respective filter. In some embodiments, thefourth plurality of filters includes one or more of: a heart problemfilter, a blood pressure filter, a stroke filter, a liver diseasefilter, a kidney disease filter, a retinitis pigmentosa filter, astomach ulcer filter, a bleeding problem filter, a genital abnormalityfilter, a blood cell disorder, and a drug interaction filter.

The method continues by obtaining acknowledgment from the subject forthe warning issued to the subject by any filter in the fourth pluralityof filters. When the re-fulfillment process is not already terminated bythe firing of a filter in the third plurality of filters and the subjecthas acknowledged each warning associated with each filter in the fourthplurality of filters that was fired, the method continues with are-fulfillment procedure.

In some embodiments, the method includes storing an indication in thesubject profile of a re-order for the PDE₅ inhibitor pharmaceuticalcomposition, communicating an over-the-counter drug facts label for thePDE₅ inhibitor pharmaceutical composition to the subject, andauthorizing, upon confirmation from the subject that theover-the-counter drug facts label has been received and read, a re-orderprovision of the PDE₅ inhibitor pharmaceutical composition to thesubject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary system topology that includes a PDE₅inhibitor pharmaceutical composition over-the-counter (OTC) dispensingdevice for qualifying a human subject for over-the-counter delivery of aPDE₅ inhibitor pharmaceutical composition to treat erectile dysfunction,a data collection device for collecting subject data, one or more userdevices associated with human subjects, and one or more dispensarydestinations for distributing the PDE₅ inhibitor pharmaceuticalcomposition over-the-counter, where the above-identified components areinterconnected, optionally through a communications network, inaccordance with an embodiment of the present disclosure.

FIG. 2 illustrates an example device for qualifying a human subject fordelivery of a PDE₅ inhibitor pharmaceutical composition over-the-counterto treat erectile dysfunction in accordance with various embodiments ofthe present disclosure.

FIGS. 3A, 3B and 3C collectively illustrate an example device associatedwith a human subject for qualifying the human subject forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction, in accordance with an embodiment of thepresent disclosure, where it will be appreciated that the example deviceof FIGS. 3A and 3B works in conjunction with the device of FIG. 2 toperform the methods illustrated in FIGS. 4 through 8 in some embodimentsby, for instance providing the device of FIG. 2 with survey resultsand/or the results of firing filters of the present disclosure againstsuch survey results but that, in alternative embodiments, the device ofFIG. 2 performs all the methods of the present disclosure and the deviceof FIGS. 3A and 3B is not used. In still further alternativeembodiments, the device of FIGS. 3A and 3B performs the methods of thepresent disclosure and the device of FIG. 2 is not used.

FIGS. 4A, 4B, 4C, 4D, 4E, 4F, 4G, 4H, and 4I collectively provide a flowchart of processes for qualifying a human subject for over-the-counterdelivery of a PDE₅ inhibitor pharmaceutical composition to treaterectile dysfunction, where elements in dashed boxes are optional, inaccordance with various embodiments of the present disclosure.

FIGS. 5A, 5B, 5C, 5D, and 5E illustrate example survey questions forobtaining survey results, in accordance with an embodiment of thepresent disclosure.

FIG. 6 illustrates feedback from a first survey in accordance with anembodiment of the present disclosure.

FIGS. 7A, 7B, 7C, and 7D collectively illustrate an example method forqualifying a subject for an over-the-counter provision of a PDE5inhibitor pharmaceutical composition in accordance with an embodiment ofthe present disclosure.

FIGS. 8A, 8B, 8C, 8D, and 8E collectively illustrate an example methodfor qualifying a subject for a refill of an over-the-counter provisionPDE₅ inhibitor pharmaceutical composition in accordance with anembodiment of the present disclosure.

In the figures, reference numbers refer to the same or equivalent partsof the present invention throughout the several figures of the drawing.

DETAILED DESCRIPTION

Erectile dysfunction is a growing health problem, in the United Statesand worldwide. Although erectile dysfunction can be effectively treatedand/or prevented using established pharmaceutical compositions, accessto these drugs is hindered by to the requirement for a prescription, asmany individuals do not have adequate access and/or avoid the healthcaresystem for a variety of reasons. Accordingly, many people are notmanaging their erectile dysfunction or conditions related to erectiledysfunction appropriately. While over-the-counter alternatives to theseprescription pharmaceuticals would increase access to thesecompositions, thereby improving population management of erectiledysfunction around the world, patients often have difficultyself-selecting themselves for an appropriate over-the-countermedication. Because inappropriate use of these drugs can result inineffective treatment and/or serious side-effects, better methods forselecting for, and treating patients with, other-the-counter erectiledysfunction medications are needed. The present disclosure provides,among other aspects, methods, systems, and computer readable media thatsolve these problems.

Reference will now be made in detail to implementations, examples ofwhich are illustrated in the accompanying drawings. In the followingdetailed description of implementations, numerous specific details areset forth in order to provide a thorough understanding of the presentinvention. However, it will be apparent to one of ordinary skill in theart that the present invention may be practiced without these specificdetails.

It will also be understood that, although the terms first, second, etc.may be used herein to describe various elements, these elements shouldnot be limited by these terms. These terms are only used to distinguishone element from another. For example, a first filter could be termed asecond filter, and, similarly, a second filter could be termed a firstfilter, without departing from the scope of the present disclosure. Thefirst filter and the second filter are both filters, but they are notthe same filter.

The terminology used in the present disclosure is for the purpose ofdescribing particular embodiments only and is not intended to belimiting of the invention. As used in the description of the inventionand the appended claims, the singular forms “a,” “an,” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise. It will also be understood that the term “and/or”as used herein refers to and encompasses any and all possiblecombinations of one or more of the associated listed items. It will befurther understood that the terms “comprises” and/or “comprising,” whenused in this specification, specify the presence of stated features,integers, steps, operations, elements, and/or components, but do notpreclude the presence or addition of one or more other features,integers, steps, operations, elements, components, and/or groupsthereof.

As used herein, the term “if” may be construed to mean “when” or “upon”or “in response to determining” or “in response to detecting,” dependingon the context. Similarly, the phrase “if it is determined” or “if [astated condition or event] is detected” may be construed to mean “upondetermining” or “in response to determining” or “upon detecting [thestated condition or event]” or “in response to detecting [the statedcondition or event],” depending on the context.

As used herein, the term “over-the-counter” means to provide by retailpurchase, subject to the constraints disclosed herein, but without aprescription or license from a physician or medical practitioner.

As used herein, the term “pharmaceutical compound” refers to anyphysical state of a material. Pharmaceutical compounds include capsules,tablets, liquids, topical formulations, and inhaled formulations.

As used herein, the term “contraindication” refers to a condition thatmakes a treatment, e.g., over-the-counter use of a cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition,inadvisable. Contraindications include physical characteristics of asubject, e.g., is not a male or has a liver disease, and contemporaneousdrug use, e.g., PDE₅ inhibitor pharmaceutical composition use. In thepresent context, identification of a contraindication fires a filter ofa first category class, which prevents authorizing provision of a PDE₅inhibitor pharmaceutical composition, in accordance with someimplementations of the methods, systems, and software disclosed herein.

As used herein, the term “risk factor” refers to a condition that makesa treatment, e.g., over-the-counter use of a PDE₅ inhibitorpharmaceutical composition, possibly inadvisable. Risk factors includephysical characteristics of a subject, e.g., a blood pressure reading,and contemporaneous drug use, e.g., use of a vasodilator medication. Inthe present context, identification of a risk factor fires a filter of asecond category class, which prevents authorizing provision of a PDE₅inhibitor pharmaceutical composition without confirmation that thesubject has discussed the risk factor with a medical professional, inaccordance with some implementations of the methods, systems, andsoftware disclosed herein.

As used herein, “drug interactions,” e.g., with a PDE₅ inhibitor,include pharmacokinetic drug interactions and pharmacodynamics druginteractions. Generally, a pharmacokinetic drug interaction is aninteraction between two drugs (e.g., a PDE₅ inhibitor and a second drug)that result in alterations in the absorption, transport, distribution,metabolism, and/or excretion of either drug. Generally, apharmacokinetic drug interaction is an interaction between two drugs(e.g., a PDE₅ inhibitor and a second drug) that result in a directchange in the effect or either drug. For a more comprehensive summary ofpharmacokinetic drug interactions and pharmacodynamics druginteractions, see, Cascorbi, I, Dtsch Arztebl Int., 109(33-34):546-55(2012), the content of which is hereby incorporated by reference.

In the context of the present disclosure, classification of a conditionas either a contraindication or a risk factor is specific to aparticular identity and dose of a PDE₅ inhibitor pharmaceuticalcomposition being authorized for over-the-counter use. Classification ofa particular condition, e.g., contemporaneous PDE₅ inhibitorpharmaceutical composition use, may vary between different PDE₅inhibitor pharmaceutical compositions (e.g., it may be classified as acontraindication for a first PDE₅ inhibitor, a risk factor for a secondPDE₅ inhibitor, and/or neither for a third PDE₅ inhibitor). Likewise, aparticular condition may be classified as a contraindication for use ofa particular PDE₅ inhibitor at a first over-the-counter dosage,classified as a risk factor for the same particular PDE₅ inhibitor at asecond (e.g., lower) over-the-counter dosage, and/or classified asneither for the same particular PDE₅ inhibitor at a third (e.g., lowest)over-the-counter dosage.

As used herein, whether a subject “has developed” a condition sincereceiving their last provision of a PDE5 inhibitor refers to bothconditions that are new to the subject, i.e., a condition that thesubject did not have at the time they received their last provision ofthe PDE5, and conditions that have been newly diagnosed, regardless ofwhether the condition existed when the subject received their lastprovision of the PDE5 inhibitor, i.e., a condition that the subject wasnot aware of when they received their last provision of the PDE5inhibitor.

The term “alkyl,” by itself or as part of another substituent, means,unless otherwise stated, a straight or branched chain, or cyclichydrocarbon radical, or combination thereof, which may be fullysaturated, mono- or polyunsaturated and can include di-, tri- andmultivalent radicals, having the number of carbon atoms designated (e.g.C₁-C₁₀ means one to ten carbons). Examples of saturated hydrocarbonradicals include groups such as methyl, ethyl, n-propyl, isopropyl,n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl,cyclopropylmethyl, homologs and isomers of, for example, n-pentyl,n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group isone having one or more double bonds or triple bonds. Examples ofunsaturated alkyl groups include vinyl, 2-propenyl, crotyl,2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl),ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs andisomers. The term “alkyl,” unless otherwise noted, is also meant tooptionally include those derivatives of alkyl defined in more detailbelow, such as “heteroalkyl.” Alkyl groups that are limited tohydrocarbon groups are termed “homoalkyl”. Exemplary alkyl groupsinclude the monounsaturated C₉₋₁₀, oleoyl chain or the diunsaturatedC_(9-10, 12-13) linoeyl chain.

The term “alkylene” by itself or as part of another substituent means adivalent radical derived from an alkane, as exemplified, but notlimited, by —CH₂CH₂CH₂CH₂—, and further includes those groups describedbelow as “heteroalkylene.” Typically, an alkyl (or alkylene) group willhave from 1 to 24 carbon atoms, with those groups having 10 or fewercarbon atoms being preferred in the present invention. A “lower alkyl”or “lower alkylene” is a shorter chain alkyl or alkylene group,generally having eight or fewer carbon atoms.

The terms “alkoxy,” “alkylamino” and “alkylthio” (or thioalkoxy) areused in their conventional sense, and refer to those alkyl groupsattached to the remainder of the molecule via an oxygen atom, an aminogroup, or a sulfur atom, respectively.

The terms “cycloalkyl” and “heterocycloalkyl,” by themselves or incombination with other terms, represent, unless otherwise stated, cyclicversions of “alkyl” and “heteroalkyl”, respectively. Additionally, forheterocycloalkyl, a heteroatom can occupy the position at which theheterocycle is attached to the remainder of the molecule. Examples ofcycloalkyl include cyclopentyl, cyclohexyl, 1-cyclohexenyl,3-cyclohexenyl, cycloheptyl, and the like. Further exemplary cycloalkylgroups include steroids, e.g., cholesterol and its derivatives. Examplesof heterocycloalkyl include 1-(1,2,5,6-tetrahydropyridyl),1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl,3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl,tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl,2-piperazinyl, and the like.

The terms “halo” or “halogen,” by themselves or as part of anothersubstituent, mean, unless otherwise stated, a fluorine, chlorine,bromine, or iodine atom. Additionally, terms such as “haloalkyl,” aremeant to include monohaloalkyl and polyhaloalkyl. For example, the term“halo(C₁-C₄)alkyl” is mean to include, but not be limited to,trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, andthe like.

The term “aryl” means, unless otherwise stated, a polyunsaturated,aromatic, substituent that can be a single ring or multiple rings(preferably from 1 to 3 rings), which are fused together or linkedcovalently. The term “heteroaryl” refers to aryl substituent groups (orrings) that contain from one to four heteroatoms selected from N, O, S,Si and B, wherein the nitrogen and sulfur atoms are optionally oxidized,and the nitrogen atom(s) are optionally quaternized. An exemplaryheteroaryl group is a six-membered azine, e.g., pyridinyl, diazinyl andtriazinyl. A heteroaryl group can be attached to the remainder of themolecule through a heteroatom. Non-limiting examples of aryl andheteroaryl groups include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl,1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl,4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl,5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl,4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl,5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl,5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, and6-quinolyl. Substituents for each of the above noted aryl and heteroarylring systems are selected from the group of acceptable substituentsdescribed below.

For brevity, the term “aryl” when used in combination with other terms(e.g., aryloxy, arylthioxy, arylalkyl) includes aryl, heteroaryl andheteroarene rings as defined above. Thus, the term “arylalkyl” is meantto include those radicals in which an aryl group is attached to an alkylgroup (e.g., benzyl, phenethyl, pyridylmethyl and the like) includingthose alkyl groups in which a carbon atom (e.g., a methylene group) hasbeen replaced by, for example, an oxygen atom (e.g., phenoxymethyl,2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like).

Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “aryl, and“heteroaryl”) are meant to optionally include both substituted andunsubstituted forms of the indicated species. Exemplary substituents forthese species are provided below.

Substituents for the alkyl and heteroalkyl radicals (including thosegroups often referred to as alkylene, alkenyl, heteroalkylene,heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, andheterocycloalkenyl) are generically referred to as “alkyl groupsubstituents,” and they can be one or more of a variety of groupsselected from, but not limited to: H, substituted or unsubstituted aryl,substituted or unsubstituted heteroaryl, substituted or unsubstitutedheterocycloalkyl, —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′, halogen,—SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO₂R′, —CONR′R″, —OC(O)NR′R″,—NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)₂R′, —NR— C(NR′R″R′″)═NR″″, NRC(NR′R″)═NR′″, —S(O)R′, —S(O)₂R′, —S(O)₂NR′R″, NRSO₂R′, —CN and —NO₂ ina number ranging from zero to (2m′+1), where m′ is the total number ofcarbon atoms in such radical. R′, R″, R′″ and R″″ each preferablyindependently refer to hydrogen, substituted or unsubstitutedheteroalkyl, substituted or unsubstituted aryl, e.g., aryl substitutedwith 1-3 halogens, substituted or unsubstituted alkyl, alkoxy orthioalkoxy groups, or arylalkyl groups. When a compound of the inventionincludes more than one R group, for example, each of the R groups isindependently selected as are each R′, R″, R′″ and R″″ groups when morethan one of these groups is present. When R′ and R″ are attached to thesame nitrogen atom, they can be combined with the nitrogen atom to forma 5-, 6-, or 7-membered ring. For example, —NR′R″ is meant to include,but not be limited to, 1-pyrrolidinyl and 4-morpholinyl. From the abovediscussion of substituents, one of skill in the art will understand thatthe term “alkyl” is meant to include groups including carbon atoms boundto groups other than hydrogen groups, such as haloalkyl (e.g., —CF₃ and—CH₂CF₃) and acyl (e.g., —C(O)CH₃, —C(O)CF₃, —C(O)CH₂OCH₃, and thelike). These terms encompass groups considered exemplary “alkyl groupsubstituents,” which are components of exemplary “substituted alkyl” and“substituted heteroalkyl” moieties.

Similar to the substituents described for the alkyl radical,substituents for the aryl heteroaryl and heteroarene groups aregenerically referred to as “aryl group substituents.” The substituentsare selected from, for example: groups attached to the heteroaryl orheteroarene nucleus through carbon or a heteroatom (e.g., P, N, O, S,Si, or B) including, without limitation, substituted or unsubstitutedalkyl, substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted or unsubstituted heterocycloalkyl, —OR′, ═O,═NR′, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′,—CO₂R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, NR′ C(O)NR″R′″, —NR″ C(O)₂R′,NR—C(NR′R″R′″)═NR″″, NR C(NR′R″)═NR′″, —S(O)R′, —S(O)₂R′, —S(O)₂NR′R″,NRSO₂R′, —CN and —NO₂, —R′, —N₃, —CH(Ph)₂, fluoro(C₁-C₄)alkoxy, andfluoro(C₁-C₄)alkyl, in a number ranging from zero to the total number ofopen valences on the aromatic ring system. Each of the above-namedgroups is attached to the heteroarene or heteroaryl nucleus directly orthrough a heteroatom (e.g., P, N, O, S, Si, or B); and where R′, R″, R′″and R″″ are preferably independently selected from hydrogen, substitutedor unsubstituted alkyl, substituted or unsubstituted heteroalkyl,substituted or unsubstituted aryl and substituted or unsubstitutedheteroaryl. When a compound of the invention includes more than one Rgroup, for example, each of the R groups is independently selected asare each R′, R″, R′″ and R″″ groups when more than one of these groupsis present.

As used herein, the term “heteroatom” includes oxygen (O), nitrogen (N),sulfur (S) and silicon (Si), boron (B) and phosphorous (P).

The symbol “R” is a general abbreviation that represents a substituentgroup that is selected from H, substituted or unsubstituted alkyl,substituted or unsubstituted heteroalkyl, substituted or unsubstitutedaryl, substituted or unsubstituted heteroaryl, and substituted orunsubstituted heterocycloalkyl groups.

The term “salt(s)” includes salts of the compounds prepared by theneutralization of acids or bases, depending on the particular ligands orsubstituents found on the compounds described herein. When compounds ofthe present invention contain relatively acidic functionalities, baseaddition salts can be obtained by contacting the neutral form of suchcompounds with a sufficient amount of the desired base, either neat orin a suitable inert solvent. Examples of base addition salts includesodium, potassium calcium, ammonium, organic amino, or magnesium salt,or a similar salt. Examples of acid addition salts include those derivedfrom inorganic acids like hydrochloric, hydrobromic, nitric, carbonic,monohydrogencarbonic, phosphoric, monohydrogenphosphoric,dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, orphosphorous acids, and the like, as well as the salts derived fromrelatively nontoxic organic acids like acetic, propionic, isobutyric,butyric, maleic, malic, malonic, benzoic, succinic, suberic, fumaric,lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric,tartaric, methanesulfonic, and the like. Certain specific compounds ofthe present invention contain both basic and acidic functionalities thatallow the compounds to be converted into either base or acid additionsalts. Hydrates of the salts are also included.

It is understood that, in any compound described herein having one ormore chiral centers, if an absolute stereochemistry is not expresslyindicated, then each center may independently be of R-configuration orS-configuration or a mixture thereof. Thus, the compounds providedherein may be enantiomerically pure or be stereoisomeric mixtures. Inaddition, it is understood that, in any compound described herein havingone or more double bond(s) generating geometrical isomers that can bedefined as E or Z, each double bond may independently be E or Z amixture thereof. Likewise, it is understood that, in any compounddescribed, all tautomeric forms are also intended to be included.

In one aspect, the present disclosure conducts a survey of a subject toobtain survey results in order to determine if the subject qualifies foran over-the-counter (OTC) PDE₅ inhibitor pharmaceutical composition forthe treatment of erectile dysfunction. The survey results are used asthe basis for running filters of a first category class. If thetriggering conditions of any of the filters in the first category classare fired, the subject does not qualify for the OTC PDE₅ inhibitorpharmaceutical composition. The survey results are also used as thebasis for running filters of a second category class. If the triggeringconditions of any of the filters in the second category class are fired,the subject is provided with warning messages associated with therespective filters of the second category class that have been fired. Ifnone of the filters in the first category class are fired and thesubject successfully addresses the warning messages associated with therespective filters of the second category class that have been fired afulfillment process is initiated for OTC delivery of the PDE₅ inhibitorpharmaceutical composition.

FIG. 1 illustrates an example of an integrated system 48 for conductingone or more surveys of subjects in order to qualifying the subjects forOTC delivery of a PDE₅ inhibitor pharmaceutical composition. Theintegrated system 48 includes one or more connected user devices 102.The user devices 102 are configured for entering survey data and makingrequests for the PDE₅ inhibitor pharmaceutical composition. The system48 also includes one or more dispensary destination devices 104 that areconfigured to receive instructions in order to provide the PDE₅inhibitor pharmaceutical composition to qualifying subjects.Furthermore, the system 48 includes a cGMP-specific phosphodiesterase 5(PDE₅) inhibitor pharmaceutical composition over-the-counter (OTC)dispensing device 250 and one or more data collection devices 200 thatare configured for collecting subject data.

Throughout the present disclosure, the data collection device 200 andthe PDE₅ inhibitor pharmaceutical composition OTC dispensing device 250will be referenced as separate devices solely for purposes of clarity.That is, the disclosed functionality of the data collection device 200and the disclosed functionality of the PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device 250 are contained in separate devicesas illustrated in FIG. 1 . However, it will be appreciated that, infact, in some embodiments, the disclosed functionality of the datacollection device 200 and the disclosed functionality of the PDE₅inhibitor pharmaceutical composition OTC dispensing device 250 arecontained in a single device.

With the integrated system 48, survey results from the subjects are runagainst a first plurality of filters (e.g., filter 216-1, filter 216-2,filter 216-3, etc.) When a filter in the first plurality of filters(e.g., filter 216) is fired for a respective subject, the respectivesubject is deemed not qualified for the PDE₅ inhibitor pharmaceuticalcomposition. The survey results are also run against a second pluralityof filters (e.g., filter 222-1, filter 222-2, filter 222-6, etc.) When arespective filter in the second plurality is fired for a respectivesubject, the respective subject is provided with a warning (e.g., filterwarning 226) associated with the respective filter. In some embodimentsthe survey results are run against the first plurality of filters andthe second plurality of filters concurrently. In some embodiments thesurvey results are run against the first plurality of filters and thenagainst the second plurality of filters. The method enabled by theintegrated system 48 proceeds to a fulfillment process when no filter inthe first plurality fires and the subject has acknowledged, or otherwisesuccessfully addressed, each warning associated with each filter in thesecond plurality of filters that fired. As part of the fulfillmentprocess, the composition order is stored (e.g., in a user profile 234associated with the subject to receive the drug), a drug facts label(e.g., drug facts label 230) for the PDE₅ inhibitor is communicated tothe qualifying subject. Upon subject confirmation that the label hasbeen read, authorization is granted to dispense the PDE₅ inhibitor.

Referring to FIG. 1 , the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 qualifies a subject for over-the-counter deliveryof a PDE₅ inhibitor pharmaceutical composition to treat erectiledysfunction. To accomplish this, the data collection device 200, whichis in electrical communication with the PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device 250, receives survey resultsoriginating from one or more user devices 102 associated withcorresponding subjects. In some embodiments, the data collection device200 receives such survey results directly from the user devices 102. Forinstance, in some embodiments the data collection device 200 receivesthis data wirelessly through radio-frequency signals. In someembodiments, such signals are in accordance with an 802.11 (Wi-Fi),Bluetooth, or ZigBee standard. In some embodiments, the data collectiondevice 200 receives such data directly, analyzes the data, and passesthe analyzed data to the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250.

In some embodiments, the data collection device 200 and/or the PDE₅inhibitor pharmaceutical composition OTC dispensing device 250 is notproximate to the subject and/or does not have wireless capabilities orsuch wireless capabilities are not used for the purpose of acquiringsurvey results. In some embodiments, a communication network 106 may beused to survey questions (e.g., survey questions 208, 212) from the PDE₅inhibitor pharmaceutical composition OTC dispensing device 250 to userdevices 102 and the answers to such survey questions from the userdevices 102 to the data collection device 200 and/or the PDE₅ inhibitorpharmaceutical composition OTC dispensing device 250. Further, in someembodiments the communication network 106 is used to communicateauthorization to dispense the PDE₅ inhibitor survey questions from thePDE₅ inhibitor pharmaceutical composition OTC dispensing device 250 todispensary destination devices 104.

Examples of networks 106 include the World Wide Web (WWW), an intranetand/or a wireless network, such as a cellular telephone network, awireless local area network (LAN) and/or a metropolitan area network(MAN), and other devices by wireless communication. The wirelesscommunication optionally uses any of a plurality of communicationsstandards, protocols and technologies, including Global System forMobile Communications (GSM), Enhanced Data GSM Environment (EDGE),high-speed downlink packet access (HSDPA), high-speed uplink packetaccess (HSUPA), Evolution, Data-Only (EV-DO), HSPA, HSPA+, Dual-CellHSPA (DC-HSPDA), long term evolution (LTE), near field communication(NFC), wideband code division multiple access (W-CDMA), code divisionmultiple access (CDMA), time division multiple access (TDMA), Bluetooth,Wireless Fidelity (Wi-Fi) (e.g., IEEE 802.11a, IEEE 802.11ac, IEEE802.11ax, IEEE 802.11b, IEEE 802.11g and/or IEEE 802.11n), voice overInternet Protocol (VoIP), Wi-MAX, a protocol for e-mail (e.g., Internetmessage access protocol (IMAP) and/or post office protocol (POP)),instant messaging (e.g., extensible messaging and presence protocol(XMPP), Session Initiation Protocol for Instant Messaging and PresenceLeveraging Extensions (SIMPLE), Instant Messaging and Presence Service(IMPS)), and/or Short Message Service (SMS), or any other suitablecommunication protocol, including communication protocols not yetdeveloped as of the filing date of the present disclosure.

Of course, other topologies of the system 48 are possible. For instance,rather than relying on a communications network 106, the one or moreuser devices 102 and the one or more dispensary destination devices 104may communicate directly to the data collection device 200 and/or thePDE₅ inhibitor pharmaceutical composition OTC dispensing device 250.Further, the data collection device 200 and/or the PDE₅ inhibitorpharmaceutical composition OTC dispensing device 250 may constitute aportable electronic device, a server computer, or in fact constituteseveral computers that are linked together in a network, be a virtualmachine in a cloud computing context, be a container in a cloud computercontext, or a combination thereof. As such, the exemplary topology shownin FIG. 1 merely serves to describe the features of an embodiment of thepresent disclosure in a manner that will be readily understood to one ofskill in the art.

Turning to FIG. 2 with the foregoing in mind, an exemplary PDE₅inhibitor pharmaceutical composition OTC dispensing device 250configured for determining whether a subject is qualified for OTCdelivery of a PDE₅ inhibitor is depicted. Referring to FIG. 2 , intypical embodiments, the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 comprises one or more computers. For purposes ofillustration in FIG. 2 , the PDE₅ inhibitor pharmaceutical compositionOTC dispensing device 250 is represented as a single computer thatincludes all of the functionality for qualifying a human subject forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction. However, the present disclosure is notlimited thereto. In some embodiments, the functionality for qualifying ahuman subject for over-the-counter delivery of a PDE₅ inhibitorpharmaceutical composition to treat erectile dysfunction is spreadacross any number of networked computers and/or resides on each ofseveral networked computers, is hosted on one or more virtual machinesat a remote location accessible across the communications network 106,and/or is hosted on one or more containers at a remote locationaccessible across the communications network 106. One of skill in theart will appreciate that any of a wide array of different computertopologies are used for the application and all such topologies arewithin the scope of the present disclosure.

The PDE₅ inhibitor pharmaceutical composition OTC dispensing device 250of FIG. 2 is configured to conduct a first survey (e.g., usingassessment module 252 to perform an initial qualification of the subjectfor provision of a PDE₅ inhibitor pharmaceutical composition) and/or asecond survey (e.g., using reassessment module 254 to perform are-qualification of the subject for provision of a PDE₅ inhibitorpharmaceutical composition). The first survey (e.g., the assessment)comprises a variety of questions 208, 212 associated with filters 216,222 within a plurality of filters of the first filter category class214-1 and a plurality of filters in the second filter category class220-1, respectively. Answers to the questions in the first surveyreceived by the device are run against filters of a first category class214-1 and filters of a second category class 220-1 within the first andsecond pluralities of filters 216, 222, respectively. Similarly, thesecond survey (e.g., the re-assessment) also comprises a variety ofquestions associated with filters 216, 222 within a plurality of filtersof a first category class 214-2 and a plurality of filters of a secondcategory class 220-2, respectively. Answers to the questions in thesecond survey received by the device are run against filters of a firstcategory class 214-2 and filters of a second category class 220-2, e.g.,within the first and second pluralities of filters, respectively.Filters 216 of the first filter category class 214 are configured toterminate the qualification process when fired. Filters 222 of thesecond filter category class 220 are configured to provide the subjectwith a warning associated with a corresponding survey question. In otherwords, the device of FIG. 2 is configured to accumulate results from asurvey (e.g., survey questions 208 and survey questions 212) and run theresults against corresponding filters (e.g., filters 216 and filters222, respectively) in order to determine if a subject is qualified forOTC delivery of a PDE₅ inhibitor pharmaceutical composition.

In the present disclosure, a plurality of filters refers to a series, orset, or filters in either the first filter category class or the secondcategory class. For instance, in some embodiments, a plurality offilters of the first filter category class 214 can comprise any subsetof filters 216 of the first filter category class. As an example, insome embodiments a plurality of filters of the first category classcomprises filters 216-1, 216-2, 216-3, . . . , 216-i, or any combinationthereof. Similarly, a plurality of filters of the second filter categoryclass 220 can comprise any set of filters 222 of the second filtercategory class. Moreover, in some embodiments a plurality of filters ofthe second category class comprises filters 222-1, 222-2, 222-3, . . . ,222-i, or any combination thereof.

Continuing to refer to FIG. 2 , in some embodiments, the dispensingdevice 250 comprises one or more processing units (CPU's) 274, a networkor other communications interface 284, a memory 192 (e.g., random accessmemory), one or more magnetic disk storage and/or persistent devices 290optionally accessed by one or more controllers 288, one or morecommunication busses 213 for interconnecting the aforementionedcomponents, a user interface 278, the user interface 278 including adisplay 282 and input 280 (e.g., keyboard, keypad, touch screen), and apower supply 276 for powering the aforementioned components. In someembodiments, data in memory 192 is seamlessly shared with non-volatilememory 290 using known computing techniques such as caching. In someembodiments, memory 192 and/or memory 290 includes mass storage that isremotely located with respect to the central processing unit(s) 274. Inother words, some data stored in memory 192 and/or memory 290 may infact be hosted on computers that are external to the PDE₅ inhibitorpharmaceutical composition OTC dispensing device 250 but that can beelectronically accessed by the PDE₅ inhibitor pharmaceutical compositionOTC dispensing device 250 over an Internet, intranet, or other form ofnetwork or electronic cable (illustrated as element 106 in FIG. 2 )using network interface 284.

In some embodiments, the memory 192 of the PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device 250 stores one or more of:

-   -   an operating system 202 that includes procedures for handling        various basic system services;    -   an assessment module 252 for qualifying a subject for an initial        over-the-counter delivery of a PDE₅ inhibitor pharmaceutical        composition to treat erectile dysfunction, by communicating        survey questions, obtaining results therefrom, and applying the        results to qualifying filters, the assessment module including:        -   a first filter category class 214-1, including filters 216            (e.g., a first plurality of filters), each respective filter            216 in the first filter category class 214-1 associated with            one or more survey questions 208 and one or more triggering            conditions 218;        -   a second filter category class 220-1, including filters 222            (e.g., a second plurality of filters), each respective            filter 222 in the second filter category class 220-1            associated with one or more survey questions 208, triggering            conditions 224, and warnings 226;    -   a fulfillment module 228-1 for executing a fulfillment process        when no filter 216 in the first filter category class 214-1 has        been fired for a subject and the subject has acknowledged each        warning 226 associated with each filter 222 in the second filter        category class 220-1 that was fired as a result of answers by        the subject to the survey questions 208, where the fulfillment        process includes communicating an over-the-counter drug facts        label 230 for the PDE₅ inhibitor pharmaceutical composition to        the subject and receiving confirmation from the subject that the        over-the-counter drug facts label has been received and read;    -   a reassessment module 254 for qualifying a subject for a        subsequent over-the-counter delivery of a PDE₅ inhibitor        pharmaceutical composition to treat erectile dysfunction, by        communicating survey questions, obtaining results therefrom, and        applying the results to qualifying filters, the assessment        module including:        -   a first filter category class 214-2, including filters 216            (e.g., a third plurality of filters), each respective filter            216 in the first filter category class 214-2 associated with            one or more survey questions 208 and one or more triggering            conditions 218;        -   a second filter category class 220-2, including filters 222            (e.g., a second plurality of filters), each respective            filter 222 in the second filter category class 220-2            associated with one or more survey questions 208, triggering            conditions 224, and warnings 226;    -   a re-fulfillment module 228-2 for executing a re-fulfillment        process when no filter 216 in the first filter category class        214-2 has been fired for a subject and the subject has        acknowledged each warning 226 associated with each filter 222-2        in the second filter category class 220 that was fired as a        result of answers by the subject to the survey questions 212,        where the fulfillment process includes communicating an        over-the-counter drug facts label 230 for the PDE₅ inhibitor        pharmaceutical composition to the subject and receiving        confirmation from the subject that the over-the-counter drug        facts label has been received and read;    -   a subject profile data store 232 comprising a user profile 234        for each of a plurality of subjects, each respective user        profile 234 including information (e.g., shipping information,        billing information, biometric information, etc.) about a        corresponding subject in the plurality of subjects, an initial        order date and destination 236, and any re-order date and the        destination 238 for the PDE₅ inhibitor pharmaceutical        composition made by the corresponding subject using the PDE₅        inhibitor pharmaceutical composition OTC dispensing device 250;    -   an adverse event module 242 for identifying and aggregating        records of adverse events associated with a plurality of        subjects, e.g., corresponding to the firing of a filter 216 in        the first filter category class 214-2 during a re-fulfillment        process;    -   a reimbursement module 240 for determining eligibility and/or        communicating an insurance claim associated with delivery of the        PDE₅ inhibitor, e.g., based on insurance information stored in a        respective user profile 234.

In some embodiments, the assessment module 252, reassessment module 254,and/or fulfillment module 228 are accessible within any browser (e.g.,phone, tablet, laptop/desktop, or smartwatch). In some embodiments, theassessment module 252, reassessment module 254, and/or fulfillmentmodule 228 run on native device frameworks, and is available fordownload onto a user device 102 running an operating system 202 such asAndroid, iOS, or WINDOWS.

In some implementations, one or more of the above identified dataelements or modules (e.g., assessment module 252, fulfillment module228-1, etc.) of the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 for qualifying a human subject forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction are stored in one or more of thepreviously described memory devices, and correspond to a set ofinstructions for performing a function described above. Theabove-identified data, modules or programs (e.g., sets of instructions)need not be implemented as separate software programs, procedures ormodules, and thus various subsets of these modules may be combined orotherwise re-arranged in various implementations. In someimplementations, the memory 192 and/or 290 optionally stores a subset ofthe modules and data structures identified above. Furthermore, in someembodiments the memory 192 and/or 290 stores additional modules and datastructures not described above.

In some embodiments, a PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 for qualifying a human subject forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction is a smart phone (e.g., an iPhone,Blackberry, etc.), a laptop, a tablet computer, a desktop computer, asmart watch, or another form of electronic device (e.g., a gamingconsole). In some embodiments, the PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device 250 is not mobile. In someembodiments, the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 is mobile.

In some embodiments, the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 is not a smart phone but rather is a tabletcomputer, desktop computer, emergency vehicle computer, or other form orwired or wireless networked device. In the interest of brevity andclarity, only a few of the possible components of the PDE₅ inhibitorpharmaceutical composition OTC dispensing device 250 are shown in FIG. 2in order to better emphasize the additional software modules that areinstalled on the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250.

FIG. 3 provides a description of a user device 102 that can be used withthe present disclosure. The user device 102 illustrated in FIG. 3 hasone or more processing units (CPU's) 374, peripherals interface 370,memory controller 368, a network or other communications interface 384,a memory 392 (e.g., random access memory), a user interface 378, theuser interface 378 including a display 382 and input 380 (e.g.,keyboard, keypad, touch screen), an optional accelerometer 317, anoptional GPS 319, optional audio circuitry 372, an optional speaker 360,an optional microphone 362, one or more optional intensity sensors 364for detecting intensity of contacts on the user device 102 (e.g., atouch-sensitive surface such as a touch-sensitive display system 382 ofthe user device 102), an optional input/output (I/O) subsystem 366, oneor more optional optical sensors 373, one or more communication busses313 for interconnecting the aforementioned components, and a powersupply 376 for powering the aforementioned components.

In some embodiments, the input 380 is a touch-sensitive display, such asa touch-sensitive surface. In some embodiments, the user interface 378includes one or more soft keyboard embodiments. The soft keyboardembodiments may include standard (e.g., QWERTY) and/or non-standardconfigurations of symbols on the displayed icons.

The user device 102 illustrated in FIG. 3 optionally includes, inaddition to accelerometer(s) 317, a magnetometer (not shown) and a GPS319 (or GLONASS or other global navigation system) receiver forobtaining information concerning the location and orientation (e.g.,portrait or landscape) of the user device 102 and/or for determining anamount of physical exertion by the subject.

It should be appreciated that the user device 102 illustrated in FIG. 3is only one example of a multifunction device that may be used forperforming a survey (e.g., first survey 206) in order to qualify forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction, and that the user device 102 optionallyhas more or fewer components than shown, optionally combines two or morecomponents, or optionally has a different configuration or arrangementof the components. The various components shown in FIG. 3 areimplemented in hardware, software, firmware, or a combination thereof,including one or more signal processing and/or application specificintegrated circuits.

Memory 392 of the user device 102 illustrated in FIG. 3 optionallyincludes high-speed random access memory and optionally also includesnon-volatile memory, such as one or more magnetic disk storage devices,flash memory devices, or other non-volatile solid-state memory devices.Access to memory 392 by other components of the PDE₅ inhibitorpharmaceutical composition OTC dispensing device 250, such as CPU(s) 374is, optionally, controlled by the memory controller 368. In someembodiments, the memory 392 of the user device 102 illustrated in FIG. 3optionally includes:

-   -   an operating system 302 that includes procedures for handling        various basic system services;    -   the assessment module 252 described above in conjunction with        the PDE₅ inhibitor composition OTC dispensing device 250;    -   the first category class 214 described above in conjunction with        the PDE₅ inhibitor pharmaceutical composition OTC dispensing        device 250 further comprising a gender filter 216-1, an age        filter 216-2, a first erectile dysfunction filter 216-3, a first        vasodilator filter 216-4, a first guanylate cyclase filter        216-5, and a PDE₅ inhibitor filter 216-6; and    -   the second category class 220 described above in conjunction        with the PDE₅ inhibitor pharmaceutical composition OTC        dispensing device 250 comprising a first heart disease filter        222-1, a first blood pressure filter 222-2, a first stroke        filter 222-3, a first liver disease filter 222-4, a first kidney        disease filter 222-5, a first retinitis pigmentosa filter 222-6,        a first vision deterioration filter 222-7, a stomach ulcer        filter 222-8, a first bleeding problem filter 222-9, a first        genital abnormality filter 222-10, a first priapism filter        222-11, a first blood cell disorder filter 222-12, and a first        drug interaction filter 222-13.

In some embodiments, the optional accelerometer 317, optional GPS 319,and/or magnetometer (not shown) of the user device 102 or suchcomponents are used to recommend to qualifying subjects one or moresuitable destinations for delivery of the PDE₅ inhibitor pharmaceuticalcomposition over-the-counter. In some embodiments, the GPS 319 is usedto determine if a subject is geographically restricted for OTC deliveryof the PDE₅ inhibitor pharmaceutical composition. Geographicalrestrictions include a subject residing outside of delivery or shippingregions, marketing restrictions, and/or government regulations.

The peripherals interface 370 can be used to couple input and outputperipherals of the device to CPU(s) 374 and memory 392. The one or moreprocessors 374 run or execute various software programs and/or sets ofinstructions stored in memory 392, such as the survey module 204, toperform various functions for the user device 102 and to process data.

In some embodiments, the peripherals interface 370, CPU(s) 374, andmemory controller 368 are, optionally, implemented on a single chip. Insome other embodiments, they are implemented on separate chips.

RF (radio frequency) circuitry of network interface 384 receives andsends RF signals, also called electromagnetic signals. In someembodiments, the survey module 204, survey questions 208/212, answers tosurvey questions 208/212, and/or the over-the-counter drug facts label230 are communicated to the subject device 102 using this RF circuitry.In some embodiments, the RF circuitry 384 converts electrical signalsto/from electromagnetic signals and communicates with communicationsnetworks and other communications devices and/or the data collectiondevice 200 and/or the PDE₅ inhibitor pharmaceutical composition OTCdispensing device 250 via the electromagnetic signals. The RF circuitry384 optionally includes well-known circuitry for performing thesefunctions, including an antenna system, an RF transceiver, one or moreamplifiers, a tuner, one or more oscillators, a digital signalprocessor, a CODEC chipset, a subscriber identity module (SIM) card,memory, and so forth. RF circuitry 384 optionally communicates with thecommunication network 106. In some embodiments, the circuitry 384 doesnot include RF circuitry and, in fact, is connected to the network 106through one or more hard wires (e.g., an optical cable, a coaxial cable,or the like).

In some embodiments, the audio circuitry 372, the optional speaker 360,and the optional microphone 362 provide an audio interface between thesubject and the user device 102. The audio circuitry 372 receives audiodata from the peripherals interface 370, converts the audio data toelectrical signals, and transmits the electrical signals to the speaker360. The speaker 360 converts the electrical signals to human-audiblesound waves. In some embodiments, the speaker 260 converts theelectrical signals to human-inaudible sound waves. The audio circuitry372 also receives electrical signals converted by the microphone 362from sound waves. The audio circuitry 372 converts the electrical signalto audio data and transmits the audio data to peripherals interface 370for processing. Audio data is, optionally, retrieved from and/ortransmitted to the memory 392 and/or the RF circuitry 384 by theperipherals interface 370.

In some embodiments, the power supply 376 optionally includes a powermanagement system, one or more power sources (e.g., battery, alternatingcurrent (AC)), a recharging system, a power failure detection circuit, apower converter or inverter, a power status indicator (e.g., alight-emitting diode (LED)) and any other components associated with thegeneration, management and distribution of power in portable devices.

In some embodiments, the user device 102 optionally also includes one ormore optical sensors 373. The optical sensor(s) 373 optionally includecharge-coupled device (CCD) or complementary metal-oxide semiconductor(CMOS) phototransistors. The optical sensor(s) 373 receive light fromthe environment, projected through one or more lens, and converts thelight to data representing an image. The optical sensor(s) 373optionally capture still images and/or video. In some embodiments, anoptical sensor is located on the back of the user device 102, oppositethe display 382 on the front of the user device 102, so that the input380 is enabled for use as a viewfinder for still and/or video imageacquisition. In some embodiments, another optical sensor 373 is locatedon the front of the user device 102 so that the subject's image isobtained (e.g., to verify the health, condition, or identity of thesubject as part of qualifying the subject for over-the-counter deliveryof a PDE₅ inhibitor pharmaceutical composition to treat erectiledysfunction), to help diagnose a subject's condition remotely, or toacquire visual physiological measurements of the subject, etc.).

As illustrated in FIG. 3 , the user device 102 preferably comprises anoperating system 302 that includes procedures for handling various basicsystem services. The operating system 302 (e.g., iOS, DARWIN, RTXC,LINUX, UNIX, OS X, WINDOWS, or an embedded operating system such asVxWorks) includes various software components and/or drivers forcontrolling and managing general system tasks (e.g., memory management,storage device control, power management, etc.) and facilitatescommunication between various hardware and software components.

In some embodiments the user device 102 is a smart phone or a smartwatch. In other embodiments, the user device 102 is not a smart phone ora smart watch but rather is a tablet computer, a desktop computer, anemergency vehicle computer, or other form or wired or wireless networkeddevice. In the interest of brevity and clarity, only a few of thepossible components of the user device 102 are shown in FIG. 3 in orderto better emphasize the additional software modules that are installedon the user device 102.

While the system 48 disclosed in FIG. 1 can work standalone, in someembodiments it can also be linked with electronic medical record systemsto exchange information in any way.

Now that details of a system 48 for qualifying a human subject forover-the-counter delivery of a PDE₅ inhibitor pharmaceutical compositionto treat erectile dysfunction have been disclosed, details regarding amethod (400), including processes and features to be performed by thesystem, in accordance with an embodiment of the present disclosure, aredisclosed with reference to FIGS. 4A through 4I. In some embodiments,such processes and features of the system are carried out by theassessment module 252, reassessment module 254, fulfillment module228-1, and/or re-fulfillment module 228-2 illustrated in FIGS. 2 and 3 .In some embodiments, the assessment module 252, reassessment module 254,fulfillment module 228-1, and/or reassessment module 228-2 are a singlesoftware module. In the flow chart, elements in dashed boxes areconsidered to be optional.

Blocks 402-408. Referring to block 402 of FIG. 4A, a goal of the presentdisclosure is to qualify subjects for over-the-counter delivery of aPDE₅ inhibitor pharmaceutical composition to treat erectile dysfunctionusing a computer system such as a PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device 250. The PDE₅ inhibitor pharmaceuticalcomposition OTC dispensing device (e.g., device 250) comprises one ormore processors (e.g., processor 274) and a memory (e.g., memory 192and/or 290). The memory stores non-transitory instructions that, whenexecuted by the one or more processors, perform a method.

Referring to block 404, in some embodiments the PDE₅ inhibitorpharmaceutical composition has the structure:

where,

R⁰ represents hydrogen, halogen or C₁₋₆ alkyl;

R¹ represents hydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, haloC₁₋₆alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl-C₁₋₃ alkyl, arylC₁₋₃ alkyl orheteroarylC₁₋₃ alkyl;

R² represents an optionally substituted mono-cyclic aromatic ringselected from benzene, thiophene, furan and pyridine or an optionallysubstituted bicyclic ring

attached to the rest of the molecule via one of the benzene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which maybe saturated or partially or fully unsaturated and comprises carbonatoms and optionally one or two heteroatoms selected from oxygen,sulphur and nitrogen; and

R³ represents hydrogen or C1-3 alkyl, or R¹ and R³ together represent a3- or 4-membered alkyl or alkenyl chain, or a pharmaceuticallyacceptable salt thereof.

Referring to blocks 406 and 408, in some embodiments the PDE₅ inhibitorpharmaceutical composition includes tadalafil. In some embodiments, thePDE₅ inhibitor includes a pharmaceutically acceptable salt of tadalafil.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes vardenafil. These, and other, PDE₅ inhibitor compositions aredescribed, for example, in Corbin, et al., “Pharmacology ofPhosphodiesterase-5 Inhibitors,” International Journal of ClinicalPractice (2002), the content of which is hereby incorporated byreference.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes any compound disclosed in U.S. Pat. No. 6,469,012, entitled“Pyrazolopyrimidinones for the Treatment of Impotence,” which is herebyincorporated by reference. In some embodiments, the PDE₅ inhibitorpharmaceutical composition includes any compound disclosed in U.S. Pat.No. 5,250,534, entitled “Pyrazolopyrimidinone Antianginal Agents,” whichis hereby incorporated by reference. In some embodiments, the PDE₅inhibitor pharmaceutical composition includes any compound disclosed inU.S. Pat. No. 6,140,329, entitled “Use of cGMP-PhosphodiesteraseInhibitors in Methods and Compositions to Treat Impotence,” which ishereby incorporated by reference.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes any compound disclosed in U.S. Pat. No. 6,566,360, entitled“2-phenyl Substituted Imidatriazinones as Phosphodiesterase Inhibitors,”which is hereby incorporated by reference. In some embodiments, the PDE₅inhibitor pharmaceutical composition includes any compound disclosed inU.S. Pat. No. 7,122,540, entitled “2-phenyl Substituted Imidatriazinonesas Phosphodiesterase Inhibitors,” which is hereby incorporated byreference.

In some embodiments, in response to receiving a first request from auser to be qualified for provision of a PDE5 inhibitor pharmaceuticalcomposition, the system creates a corresponding subject profile, e.g.,containing biographic information about the subject, e.g., one or moreof a subject name, date of birth, residence, delivery address, socialsecurity number, medical record number, insurance information, username, identification password, etc. In some embodiments, the systemregisters a subject that has not previously received an over-the-counterprovision of a PDE5 inhibitor pharmaceutical composition as a new userof the PDE5 inhibitor pharmaceutical composition, and the device willperform an initial assessment method for qualifying the subject for aprovision of the PDE5 inhibitor pharmaceutical composition, e.g.,regardless of whether the subject previously received a provision of aPDE5 inhibitor pharmaceutical composition via prescription.

In some embodiments, the system registers a subject that has previouslyreceived a provision of a PDE5 inhibitor pharmaceutical composition viaprescription as a previous user of the PDE5 inhibitor pharmaceuticalcomposition, and the device will perform a reassessment method forre-qualifying the subject for a provision of the PDE5 inhibitorpharmaceutical composition.

In some embodiments, where the subject previously received a provisionof a different PDE5 inhibitor pharmaceutical composition viaprescription, the system will perform a modified method for qualifyingthe subject for provision of the PDE5 inhibitor pharmaceuticalcomposition that accounts for differences in the contraindications andrisk factors of the two PDE5 inhibitor pharmaceutical compositions. Forexample, in response to receiving a request to qualify a user thatpreviously received a provision of a pharmaceutical compositioncontaining vardenafil via prescription, for an over-the-counterprovision of sildenafil, the system performs a modified method forre-qualifying (e.g., a reassessment) the subject for the PDE5 inhibitorpharmaceutical composition that includes a survey question andcorresponding filter relating to whether the subject has had a recentheart surgery (e.g., regardless of whether a reassessment for apharmaceutical composition containing sildenafil would normally considera subject's history of surgery), because that factor would not have beenconsidered when the subject received the prescription for thecomposition containing vardenafil.

In some embodiments, in response to receiving a second or subsequentrequest from a user to be qualified for provision of a PDE5 inhibitorpharmaceutical composition, the system registers the subject as areturning customer, e.g., when the subject has previously received anover-the-counter provision of the PDE5 inhibitor and a correspondingsubject profile 232 already exists for the subject.

In some embodiments, prior to proceeding with the qualification orre-qualification method, the device prompts (702, 704) the user toconfirm that they have adequate privacy to provide sensitive medicalinformation (e.g., prompt 704 in FIG. 7A) and/or that they are inpossession of medical information required to complete the qualificationprocess (e.g., prompt 702 to confirm that they have knowledge of therequired medical information required to completed the survey.

Blocks 410-412. Referring to block 410 of FIG. 4A, the method includesconducting a first survey of the subject thereby obtaining a firstplurality of survey results (e.g., to survey questions 208, 212 (e.g.,one or more of the survey questions set forth in Table 1). In someembodiments, the device transmits one or more survey questions to theuser, prompting a response, and then receives a response to the one ormore survey questions back from the subject. In some embodiments, thefirst survey results include, or at least indicate, some or all of thesubject characteristics listed in Table 1. For example, in someembodiments, the first plurality of survey results includes, or at leastindicates, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,or all 19 of the characteristics listed in Table 1. In one embodiment,the first survey questions 208, 212 and results include all ofcharacteristics 1-19 as provided in Table 1.

Referring to block 412, e.g., as illustrated in FIG. 7 , in someembodiments the first survey results indicate a gender of the subject(e.g., responsive to a survey 208, such as question 550, e.g., that isassociated with and/or applied to (704) a gender filter 216-1 of a firstcategory class 214-1), an age of the subject (e.g., responsive to asurvey question 208 that is associated with and/or applied to (706) anage filter 216-2 of a first category class), an erectile dysfunctionstatus of the subject (e.g., responsive to a survey question 208 that isassociated with and/or applied to (708) an erectile dysfunction filter216-3 of a first category class), whether the subject is taking anitrate or nitrite vasodilator composition (e.g., responsive to a surveyquestion 208 that is associated with and/or applied to (710) avasodilator filter 216-4 of a first category class), whether the subjectis taking a guanylate cyclase stimulator medication (e.g., responsive toa survey question 208 that is associated with and/or applied to (712) aguanylate cyclase stimulator filter 216-5 of a first category class),whether the subject is taking a PDE₅ inhibitor composition (e.g.,responsive to a survey question 208 that is associated with and/orapplied to (714) a PDE₅ inhibitor filter 216-6 of a first categoryclass), whether the subject has ever had a heart problem (e.g.,hospitalization for angina pectoris, coronary revascularization,myocardial infarction, cardiovascular death, resuscitated cardiacarrest, hospitalization for heart failure, stroke/TIA, or peripheralvascular disease) (e.g., responsive to a survey question 208 that isassociated with and/or applied to (716) a heart problem filter 222-1 ofa second category class 220-1), a blood pressure status of the subject(e.g., responsive to a survey question 208 that is associated withand/or applied to (718,720) a blood pressure filter 222-2 of a secondcategory class), whether the subject has ever had a stroke (e.g.,responsive to a survey question 208 that is associated with and/orapplied to (722) a stroke filter 222-3 of a second filter classcategory), whether the subject has a liver problem (e.g., responsive toa survey question 208 that is associated with and/or applied to (724) aliver disease filter 222-4 of a second category class), a kidneyfunction status of the subject (e.g., responsive to a survey question208 that is associated with and/or applied to (726) a kidney diseasefilter 222-5 of a second category class), whether the subject hasretinitis pigmentosa (e.g., responsive to a survey question 208 that isassociated with and/or applied to (728) a retinitis pigmentosa filter222-6 of a second category class), whether the subject has developedvision loss (e.g., responsive to a survey question 208 that isassociated with and/or applied to (730) a vision deterioration filter222-7 of a second category class), whether the subject has ever had astomach ulcer (e.g., responsive to a survey question 208 that isassociated with and/or applied to (732) a stomach ulcer filter 222-8 ofa second category class), whether the subject has a bleeding disorder(e.g., responsive to a survey question 208 that is associated withand/or applied to (734) a bleeding problem filter 222-9 of a secondcategory class), a genital status of the subject (e.g., responsive to asurvey question 208 that is associated with and/or applied to (736) agenital abnormality filter 222-10 of a second category class), whetherthe subject has ever experienced priapism (e.g., responsive to a surveyquestion 208 that is associated with and/or applied to (738) a priapismfilter 222-11 of a second category class), whether the subject has ablood cell disorder (e.g., responsive to a survey question 208 that isassociated with and/or applied to (740) a blood cell disorder filter222-12 of a second category class), and whether the subject is taking amedication that interacts with the PDE₅ inhibitor pharmaceuticalcomposition (e.g., responsive to a survey question 208 that isassociated with and/or applied to (742-752) a drug interaction filter222-13 of a second category class).

In some embodiments, the first survey includes questions that elicitresponses providing or indicating some or all of the characteristicslisted in Table 1. In some embodiments, the survey includes questionscorresponding to each of the survey results required for the methodsdescribed herein. In other embodiments, the survey includes questionscorresponding to only a subset of the survey results required for themethods described herein. In some embodiments, other survey resultsrequired for the methods described herein are acquired through othermeans (e.g., upon registration/subscription for a service associatedwith qualifying the subject for over-the-counter medication, from ahealthcare provider, from a prior survey, from a database associatedwith a pharmacy, from an electronic health record associated with thesubject, from the subject profile data store 232, etc.) For example, insome embodiments, the subject provides a personal medical identificationassociated with an insurer, a hospital, or other healthcare provider andinformation about the subject required for the methods described herein,e.g., one or more survey results, is acquired from a preexistingdatabase associated with the personal medical identification (e.g., alast cholesterol or blood pressure measurement determined for thesubject).

TABLE 1 Example subject characteristics for qualifying a subject for anover-the-counter provision of a PDE₅ inhibitor pharmaceuticalcomposition Result Example Characteristics 1 a gender of the subject 2an age of the subject 3 an erectile dysfunction status of the subject 4whether the subject is taking a nitrate or nitrite vasodilatorcomposition 5 whether the subject is taking a guanylate cyclasestimulator medication 6 whether the subject is taking a PDE₅ inhibitorcomposition 7 whether the subject has ever had a heart problem, 8 ablood pressure status of the subject 9 whether the subject has ever hada stroke 10 whether the subject has a liver problem 11 a kidney functionstatus of the subject 12 whether the subject has retinitis pigmentosa 13whether the subject has developed vision loss or hearing loss 14 whetherthe subject has ever had a stomach ulcer 15 whether the subject has ableeding disorder 16 a genital status of the subject 17 whether thesubject has ever experienced priapism 18 whether the subject has a bloodcell disorder 19 whether the subject is taking a medication thatinteracts with the PDE₅ inhibitor pharmaceutical composition

It is contemplated that, in some embodiments, any one or more of thesurvey questions 208, 212 provided in Table 1 will not be included inthe first survey (e.g., will not be used for the assessment. Forexample, in some embodiments, a characteristic associated with aparticular survey questions will be informative when qualifying asubject for one particular PDE₅ inhibitor but not for another PDE₅inhibitor.

Accordingly, it is contemplated that the first survey questions 208include any subset of survey results provided in Table 1. For brevity,all possible combinations of survey questions 208, 212 eliciting thecharacteristics provided in Table 1 are not specifically delineatedhere. However, the skilled artisan will easily be able to envision anyparticular subset of the survey questions 208, 212 that elicit thecharacteristics provided in Table 1. Likewise, the skilled artisan mayknow of other survey questions, eliciting informative subjectcharacteristics not provided in Table 1, that may be combined with anysubset of survey questions that elicit subject characteristics providedin Table 1 to form the first survey questions used in the methodsdescribed herein.

In some embodiments, the first and/or second survey is conducted bytransmitting a plurality of questions to the subject, e.g., some or allof the survey questions, and receiving answers to the plurality ofsurvey questions before applying any of the answers to respectivefilters. For example, with reference to the workflow in FIG. 7 , thedevice transmits questions relating to all of the filters of the firstcategory class, all of the filters of the second category class, or allof the filters in the workflow (e.g., as a virtual survey where all ofthe questions are displayed in a single user interface, or as a seriesof questions displayed in consecutive user interfaces). After receivinganswers to all of the survey questions, the device then applies theanswers to all of the filters (e.g., sequentially or concurrently) todetermine whether the subject is qualified to receive provision of thePDE₅ inhibitor pharmaceutical composition. In alternative embodiments,the device transmits questions relating to just those filters of thefirst category class for which it could not obtain answers to thequestions from an electronic database associated with the subject, suchas electronic health record of the subject, and just those filters ofthe second category class it could not obtain answers to the questionsfrom an electronic database associated with the subject (e.g., as avirtual survey where such unanswered questions are displayed in a singleuser interface, or as a series of questions displayed in consecutiveuser interfaces). After receiving answers to all of the surveyquestions, the device then applies the answers to all of the filters(e.g., sequentially or concurrently) to determine whether the subject isqualified to receive provision of the PDE₅ inhibitor pharmaceuticalcomposition.

In some embodiments, the first and/or second survey is conducted in aserial fashion, e.g., by transmitting a first question or a first groupof survey questions (e.g., associated with a single filter) to thesubject, receiving an answer to the single survey question or smallgroup of survey questions, and applying the answer or answers to afilter, prior to transmitting a second question or second group ofquestions to the subject. For example, with reference to the workflow inFIG. 7 , in some embodiments the device transmits a first question tothe subject, relating to the gender of the subject. After receiving theanswer to the survey question, the device applies the answer to a genderfilter (704). If the gender filter is fired (e.g., in response to anon-“male” answer), the device terminates (795-1) the process, andoptionally provides the user with a message relating to why they arebeing denied a provision of the PDE₅ inhibitor pharmaceuticalcomposition (e.g., as illustrated in FIG. 5B, message 552, advising thesubject that taking the PDE₅ inhibitor pharmaceutical compositioncreates a risk when co-administered with other drugs), a suggestion forfollowing-up with a medical professional (e.g., as illustrated in FIGS.7B and 7C, when the survey answers indicate that the subject hasexperienced priapism (738), the device terminates the process (795-2)and advises that the subject seek immediate medical attention), and/or asuggestion to make a lifestyle change, to treat their erectiledysfunction.

Blocks 414-430. Referring to block 418 of FIG. 4B, all or a portion ofthe first survey results are run against a first plurality of filters ofa first category class 214. As previously described, the first pluralityof filters includes a subset of filters 216 of the first filter categoryclass 214. When a respective filter in the first plurality of filters isfired (e.g., when a survey result indicates that a triggering condition218 has been met), the subject is deemed not qualified for delivery ofthe PDE₅ inhibitor pharmaceutical composition and the method isterminated without delivery of the PDE₅ inhibitor pharmaceuticalcomposition.

In some embodiments, e.g., when the method is terminated withoutdelivery of the PDE₅ inhibitor pharmaceutical composition, the subjectis prevented from attempting to requalify for the PDE₅ inhibitor for apredetermined period of time (e.g., the subject is locked out). In someembodiments, the subject is prevented from attempting to requalify forthe PDE₅ inhibitor after a predetermined number of qualificationattempts. In some embodiments, the subject is prevented from attemptingto requalify for the PDE₅ inhibitor after a failing to verify acommunication (e.g., failing to verify a text message sent to thesubject). This prevents the subject from abusing the systems and methodsof the present disclosure.

Referring to blocks 416-430, specific filters 216 in the first pluralityof filters and their exemplary triggering conditions 218 that cause thecorresponding filter to fire are detailed.

In some embodiments, the first plurality of filters of the firstcategory class 214 includes some or all of the filters 216 listed inTable 2. For example, in some embodiments, the first plurality offilters results includes 2, 3, 4, 5, or all 6 of the filters listed inTable 2.

TABLE 2 Example filters for contraindications associated with qualifyinga subject for an over-the-counter provision of a PDE₅ inhibitorpharmaceutical composition Filter Example Criteria 1a a gender filter 2aan age filter 3a an erectile dysfunction filter 4a a vasodilator filter5a a guanylate cyclase filter 6a a PDE₅ inhibitor filter

It is contemplated that, in some embodiments, any one or more of thefilters 216 provided in Table 2 will not be included in the firstplurality of filters. For example, in some embodiments, a characteristicassociated with a particular survey result will be informative whenqualifying a subject for one particular PDE₅ inhibitor but not foranother PDE₅ inhibitor.

Accordingly, it is contemplated that the first plurality of filtersincludes any sub-set of filters 216 provided in Table 2. Likewise, theskilled artisan may know of other filters 216, not provided in Table 2,which may be combined with any subset of the filters 216 provided inTable 2 to form the first plurality of filters results used in themethods described herein. For brevity, all possible combinations of thefilters 216 provided in Table 2 are not specifically delineated here.

Referring to block 416, in some embodiments the first plurality offilters includes a gender filter (e.g., gender filter 216-1 in FIG. 3and/or filter 1a in Table 2). In some embodiments, the gender filter isconfigured to be fired when the first plurality of survey resultsindicates that the subject is female. In some embodiments, the genderfilter is configured to be fired when the first plurality of surveyresults indicates that the subject is not male (e.g., the subject isfemale, the subject does not input a gender, the subject istransgender). If the gender filter is fired, the subject is notpermitted to obtain the PDE₅ inhibitor pharmaceutical compositionover-the-counter (e.g., the method is terminated without authorizingprovision of the PDE₅ inhibitor pharmaceutical composition to thesubject).

Referring to blocks 418-420, in some embodiments the first plurality offilters includes an age filter (e.g., age filter 216-2 in FIG. 3 and/orfilter 2a in Table 2). In some embodiments, the age filter is fired whenthe first plurality of survey results indicates that the subject has notyet reach an age of maturity, e.g., is less than eighteen years old. Ifthe age filter is fired, the subject is not permitted to obtain the PDE₅inhibitor pharmaceutical composition over-the-counter (e.g., the methodis terminated without authorizing provision of the PDE₅ inhibitorpharmaceutical composition to the subject).

Referring to block 422, in some embodiments the first plurality offilters includes an erectile dysfunction filter (e.g., erectiledysfunction filter 216-3 in FIG. 3 and/or filter 3a in Table 2). Theerectile dysfunction filter is configured to be fired at least when thefirst plurality of survey results indicates that the subject does nothave erectile dysfunction. If the erectile dysfunction filter is fired,the subject is not permitted to obtain the PDE₅ inhibitor pharmaceuticalcomposition over-the-counter (e.g., the method is terminated withoutauthorizing provision of the PDE₅ inhibitor pharmaceutical compositionto the subject).

Referring to blocks 424-426, in some embodiments the first plurality offilters includes a vasodilator filter (e.g., vasodilator filter 216-4 inFIG. 3 and/or filter 4a in Table 2). In some embodiments, thevasodilator filter is fired when the first plurality of survey resultsindicates that the subject is taking a vasodilator composition includinga nitrate or a nitrite. In some embodiments, the vasodilatorcomposition, which is capable of firing the first vasodilator filter,includes a compound selected from the group consisting of nitroglycerin,amyl nitrate, amyl nitrite, and butyl nitrate (block 426). In someembodiments, nitrate vasodilators are associated with the recreationaldrugs known as “popper(s),” which are nitric oxide donors. In someembodiments, the vasodilator filter is fired when the first plurality ofsurvey results indicates that the subject is taking a drug known as“poppers”. If the vasodilator filter is fired, the subject is notpermitted to obtain the PDE₅ inhibitor pharmaceutical compositionover-the-counter (e.g., the method is terminated without authorizingprovision of the PDE₅ inhibitor pharmaceutical composition to thesubject).

Referring to block 438, in some embodiments the first plurality offilters includes a guanylate cyclase stimulator filter (e.g., guanylatecyclase stimulator filter 216-5 in FIG. 3 and/or filter 5a in Table 2).The guanylate cyclase stimulator filter is configured to be fired atleast when the first plurality of survey results indicates that thesubject is taking a guanylate cyclase stimulator. In some embodiments,guanylate cyclase stimulators which are capable of firing the guanylatecyclase stimulator filter include riociquat and other medications thattreat pulmonary arterial hypertension and/or chronic thromboembolicpulmonary hypertension. If the guanylate cyclase stimulator filter isfired, the subject is not permitted to obtain the PDE₅ inhibitorpharmaceutical composition over-the-counter (e.g., the method isterminated without authorizing provision of the PDE₅ inhibitorpharmaceutical composition to the subject).

Referring to block 430, in some embodiments the first plurality offilters includes a PDE₅ inhibitor filter (e.g., PDE₅ inhibitor filter216-6 in FIG. 3 and/or filter 6a in Table 2). The PDE₅ inhibitor filteris configured to be fired at least when the first plurality of surveyresults indicates that the subject is taking a PDE₅ inhibitor. If thePDE₅ inhibitor filter is fired, the subject is not permitted to obtainthe PDE₅ inhibitor pharmaceutical composition over-the-counter (e.g.,the method is terminated without authorizing provision of the PDE₅inhibitor pharmaceutical composition to the subject).

Referring to block 432 of FIG. 4C, the method also includes running allor a portion of the first survey results against a second plurality offilters of a second category class 220. When a respective filter in thesecond plurality of filters is fired, the subject is provided with awarning 226 corresponding to the respective filter (e.g., filter warning226-4 corresponds to filter 222-4). In some embodiments, the warning 226is provided as a next step, e.g., prior to applying survey results toany subsequent filters, after the corresponding filter is fired. Forexample, with respect to FIG. 7C, in some embodiments, e.g., when thepriapism filter is triggered at 738, the device would provide thesubject with a warning prior to proceeding to the blood cell disorderfilter at 740, e.g., requiring the subject confirm they have discussedtheir history of priapism with a health care provider, e.g., and thehealthcare provider still recommends taking a PDE₅ inhibitorpharmaceutical composition in order to proceed with the qualification.In some embodiments the warning 226 is provided after applying surveyresults to all subsequent filters. For example, as illustrated in FIGS.7C and 7D, in some embodiments, e.g., when the priapism filter istriggered at 738, the device would proceed to the blood cell disorderfilter at 740 prior to transmitting a warning to the subject, and thentransmit all warnings corresponding to filters of the second categoryclass, at 754, after survey results have been applied to all subsequentfilters.

In some embodiments, the second plurality of filters 222 of the secondcategory class 220 includes some or all of the filters listed in Table3. For example, in some embodiments, the first plurality of filtersresults includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or all 13 of thefilters listed in Table 3. In one embodiment, the first plurality offilters includes all of filters 1-13 as provided in Table 3.

TABLE 3 Example filters for risk factors associated with qualifying asubject for an over-the-counter provision of a PDE₅ inhibitorpharmaceutical composition Filter Example Criteria 1a a heart problemfilter 2a a blood pressure filter 3a a stroke filter 4a a liver diseasefilter 5a a kidney disease filter 6a a retinitis pigmentosa filter 7a avision deterioration filter 8a a stomach ulcer filter 9a a bleedingproblem filter 10a  a genital abnormality filter 11a  a priapism filter12a  a blood cell disorder filter 13a  a drug interaction filter

Referring to blocks 434 and 436, in some embodiments, the secondplurality of filters includes a heart problem filter (e.g., heartproblem filter 222-1 in FIG. 3 and/or filter 1a in Table 3). The heartproblem filter is configured to be fired at least when the firstplurality of survey results indicate that the subject has had a heartproblem. In some embodiments, heart problems that are capable oftriggering the first heart filter include a heart attack, a heartfailure, irregular heartbeats, arrhythmia, angina, chest pain, and/ornarrowing of the aortic valve (block 436). In some embodiments, heartproblems that are capable of triggering the first heart filter includepalpitations, tachycardia, angina pectoris, myocardial infarction,and/or ventricular tachyarrhythmia. When the heart problem filter isfired, the device transmits a warning corresponding to the heart problemfilter, and requires the user to acknowledge the warning beforeauthorizing a provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 438, in some embodiments, the second plurality offilters includes a blood pressure filter (e.g., blood pressure filter222-2 in FIG. 3 and/or filter 2a in Table 3). The blood pressure filteris configured to be fired at least when the first plurality of surveyresults indicates that the subject has either low blood pressure, oruncontrolled high blood pressure. In some embodiments, the bloodpressure filter is configured to be fired at least when the firstplurality of survey results indicates that the subject has pulmonaryhypertension. In some embodiments, the low pressure, which is capable offiring the blood pressure filter, is a blood pressure less than 90/50 mmHg. In some embodiments, the low pressure, which is capable of firingthe blood pressure filter, is a blood pressure greater than 170/110 mmHg. In some embodiments, blood pressure cutoffs, or ranges, definingwhen the blood pressure filter is fired or when the blood pressurefilter is not fired are determined according to a set of healthcareguidelines, which may change over time, and/or vary on ajurisdiction-by-jurisdiction basis. For example, in the United States,the American College of Cardiology and the American Heart Associationcollaborated to provide guidance on management of high blood pressure.Whelton P K, et al., J Am Coll Cardiol., S0735-1097(17)41519-1 (2017),the contents of which are hereby expressly incorporated by reference.These guidelines change over time as medical research and advances intreatment better inform management of high and low blood pressure. Whenthe blood pressure filter is fired, the device transmits a warningcorresponding to the blood pressure filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

Referring to block 440, in some embodiments, the second plurality offilters includes a stroke filter (e.g., stroke filter 222-3 in FIG. 3and/or filter 3a in Table 3). The stroke filter is configured to befired at least when the first plurality of survey results indicates thatthe subject has had a stroke. When the stroke filter is fired, thedevice transmits a warning corresponding to the stroke filter, andrequires the user to acknowledge the warning before authorizing aprovision of the PDE₅ inhibitor pharmaceutical composition.

Referring to block 442, in some embodiments, the second plurality offilters includes a liver disease filter (e.g., liver disease filter222-4 in FIG. 3 and/or filter 4a in Table 3). In some embodiments, liverproblems that are capable of triggering the first liver disease filterinclude impaired hepatic function, acute liver failure, and cholestasis.When the liver disease filter is fired, the device transmits a warningcorresponding to the liver disease filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

Referring to block 444, in some embodiments, the second plurality offilters includes a kidney disease filter (e.g., kidney disease filter222-5 in FIG. 3 and/or filter 5a in Table 3). The kidney disease filteris configured to be fired at least when the first plurality of surveyresults indicates that the subject has a kidney problem. In someembodiments, symptoms of kidney problems which are capable of firing thekidney function filter include nausea, loss of appetite, and/or fatigue.When the kidney disease filter is fired, the device transmits a warningcorresponding to the kidney disease filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

Referring to block 446, in some embodiments, the second plurality offilters includes a retinitis pigmentosa filter (e.g., retinitispigmentosa filter 222-6 in FIG. 3 and/or filter 6a in Table 3). Theretinitis pigmentosa filter is configured to be fired at least when thefirst plurality of survey results indicates that the subject hasretinitis pigmentosa. When the retinitis pigmentosa filter is fired, thedevice transmits a warning corresponding to the retinitis pigmentosafilter, and requires the user to acknowledge the warning beforeauthorizing a provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 448, in some embodiments, the second plurality offilters includes a vision deterioration filter (e.g., visiondeterioration filter 222-7 in FIG. 3 and/or filter 7a in Table 3). Thevision deterioration filter is configured to be fired at least when thefirst plurality of survey results indicates that the subject has hadsevere vision loss. In some embodiments, severe vision loss includes anon-arteritic anterior ischemic optic neuropath (NAION). In someembodiments, severe vision loss includes visual disturbances, ocularhyperemia, visual color distortions, eye pain, eye discomfort,photophobia, an increase in intraocular pressure, and/or conjunctivitis.When the vision deterioration filter is fired, the device transmits awarning corresponding to the vision deterioration filter, and requiresthe user to acknowledge the warning before authorizing a provision ofthe PDE₅ inhibitor pharmaceutical composition.

Referring to block 450, in some embodiments, the second plurality offilters includes a stomach ulcer filter (e.g., stomach ulcer filter222-8 in FIG. 3 and/or filter 8a in Table 3). The stomach ulcer filteris configured to be fired at least when the first plurality of surveyresults indicates that the subject has had a stomach ulcer. When thestomach ulcer filter is fired, the device transmits a warningcorresponding to the stomach ulcer filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

Referring to block 452, in some embodiments, the second plurality offilters includes a bleeding problem filter (e.g., bleeding problemfilter 222-9 in FIG. 3 and/or filter 9a in Table 3). The bleedingproblem filter is configured to be fired at least when the firstplurality of survey results indicates that the subject has a bleedingdisorder. In some embodiments, bleeding disorders include significantactive peptic ulceration. When the bleeding problem filter is fired, thedevice transmits a warning corresponding to the bleeding problem filter,and requires the user to acknowledge the warning before authorizing aprovision of the PDE₅ inhibitor pharmaceutical composition.

Referring to block 454, in some embodiments, the second plurality offilters includes a genital abnormality filter (e.g., genital abnormalityfilter 222-10 in FIG. 3 and/or filter 10a in Table 3). The genitalabnormality filter is configured to be fired at least when the firstplurality of survey results indicates that the subject has an abnormalpenile shape. In some embodiments, a condition which is capable offiring the genital abnormality filter includes angulation, cavernosalfibrosis, or Peyronie's disease. When the genital abnormality filter isfired, the device transmits a warning corresponding to the genitalabnormality filter, and requires the user to acknowledge the warningbefore authorizing a provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 456 of FIG. 4D, in some embodiments, the secondplurality of filters includes a priapism filter (e.g., priapism filter222-11 in FIG. 3 and/or filter 11a in Table 3). The priapism filter isconfigured to be fired at least when the first plurality of surveyresults indicates that the subject has developed, or experienced,priapism (e.g., an erection that lasted for four hours or more). Whenthe priapism filter is fired, the device transmits a warningcorresponding to the priapism filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

Referring to block 458, in some embodiments, the second plurality offilters includes a blood cell disorder filter (e.g., blood cell disorderfilter 222-12 in FIG. 3 and/or filter 12a in Table 3). The blood celldisorder filter is configured to be fired at least when the firstplurality of survey results indicates that the subject has had a bloodcell disorder. In some embodiments, blood cell disorders include sicklecell anemia, multiple myeloma, and leukemia. When the blood celldisorder filter is fired, the device transmits a warning correspondingto the blood cell disorder filter, and requires the user to acknowledgethe warning before authorizing a provision of the PDE₅ inhibitorpharmaceutical composition.

Referring to blocks 460 and 462, in some embodiments, the secondplurality of filters includes a drug interaction filter (e.g., druginteraction filter 222-13 in FIG. 3 and/or filter 13a in Table 3). Thedrug interaction filter is configured to be fired at least when thefirst plurality of survey results indicates that the subject indicatesthat the subject is taking a medication that interacts (e.g., apharmacokinetic interaction and/or a pharmacodynamic interaction) withthe PDE₅ inhibitor pharmaceutical composition. In some embodiments, thedrug interaction filter is fired when the first plurality of surveyresults indicates that the subject is taking a medication selected fromthe group consisting of an alpha blocker (e.g., terazosin, tamsulosin,doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride and tamsulosinHCl, and silodosin), an HIV protease inhibitor (e.g., ritonavir), anantifungal medication (e.g., ketoconazole and itraconazole), anantibiotic (e.g., clarithromycin, telithromycin, and erythromycin), ablood pressure medication (e.g., a medication to treat hypertension),and an erectile dysfunction medication (block 462). When the druginteraction filter is fired, the device transmits a warningcorresponding to the drug interaction filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition.

The identity of drugs that are capable of triggering the druginteraction filter vary from one PDE₅ inhibitor to another PDE₅inhibitor. The skilled artisan will know of drugs that interact with onePDE₅ inhibitor but not another. Inclusion of a drug within the druginteraction filter is dependent upon the identity and/or the dosage ofthe PDE₅ inhibitor pharmaceutical composition being authorized forover-the-counter use.

In some implementations, a drug that interacts with a PDE₅ inhibitorpharmaceutical composition is included within a filter 216 in the firstfilter category class 214, rather than within drug interaction filter222 of the second filter category class 220. For example, according tosome implementations, a particular drug included in drug-interactionfilter 222 (e.g., as a risk factor) for a first PDE₅ inhibitorpharmaceutical composition, but included in a filter in the firstplurality of filters (e.g., as a contraindication) for a second PDE₅inhibitor pharmaceutical composition. However, a person skilled in theart will know whether to include a certain drug within drug interactionfilter 222 or as a separate filter 216 in the first plurality offilters, based on the severity and risk of the drug interaction with theparticular identity and dosage of the PDE₅ inhibitor being authorizedfor over-the-counter use.

It is contemplated that, in some embodiments, any one or more of thefilters provided in Table 3 will not be included in the second pluralityof filters. For example, in some embodiments, a characteristicassociated with a particular survey result will be informative whenqualifying a subject for one particular PDE₅ inhibitor pharmaceuticalcomposition but not for another PDE₅ inhibitor pharmaceuticalcomposition. Accordingly, it is contemplated that the second pluralityof filters includes any sub-set of filters provided in Table 3.Likewise, the skilled artisan may know of other filters, not provided inTable 3, that may be combined with any subset of the filters provided inTable 3 to form the second plurality of filters results used in themethods described herein.

Contraindications and risk factors described in the present disclosureare non-exhaustive. The skilled artisan may know of othercontraindications for a particular the PDE₅ inhibitor pharmaceuticalcomposition and/or treat risk factors as contraindications dependentupon the intended use of the PDE₅ inhibitor pharmaceutical composition.In some embodiments, contraindications for use of aprescription-strength pharmaceutical agent are treated only as riskfactors, or not at all, when qualifying a subject for a lower-dose OTCuse of a PDE5 inhibitor pharmaceutical composition.

Accordingly, it will be appreciated that the survey questions 208, 212,and filters 216, 222 applied to the survey answers thereof, may varydepending upon the PDE₅ inhibitor pharmaceutical composition beingdistributed. This is due to differences in the contraindication profilesof the various the PDE₅ inhibitor pharmaceutical compositions, e.g., dueto different drug-drug interactions, routes of drug clearance, etc. ofthe different the PDE₅ inhibitor.

Referring to block 464, in some embodiments the warning 226corresponding to a respective filter 222 in the second plurality offilters includes a prompt for the subject to indicate whether they havediscussed the risk factor underlying the respective filter in the secondplurality of filters that was fired with a health care practitioner(e.g., a licensed medical practitioner), e.g., and the health carepractitioner indicated that the subject should take a PDE₅ inhibitorpharmaceutical composition in view of the underlying risk factor.Accordingly, acknowledgement is obtained from the subject when thesubject indicates that they have discussed the risk factor underlyingthe respective filter in the second plurality of filters that was firedwith a health care provider. For example, message 602 in FIG. 6illustrates an example warning that is generic to any fired filters. Insome embodiments, the warning is specific to a particular filter (e.g.,filter warning 226 in FIG. 2 ), e.g., communicating to the user why thefilter was fired.

In some embodiments, an acknowledgment from the user is verified by thehealth care practitioner (e.g., the method requires verification inorder for authorization of the provision of the PDE₅ inhibitorpharmaceutical composition), e.g., in order to verify an accuracy of thesurvey results of the subject. In some embodiments, e.g., when theacknowledgment is verified by the heath care practitioner, the subjectis deemed a trusted subject, such that verification of future results isnot required.

Referring to block 466, the method includes obtaining acknowledgmentfrom the subject for any warning 226 issued to the subject by any filter222 in the second plurality of filters. In some embodiments,acknowledgment from the subject is a written acknowledgement, a verbalacknowledgment, or an electronic acknowledgment such as an electronicsignature. If a filter 216 in the first plurality of filters fires, thesubject is denied access to the over-the-counter PDE₅ inhibitorpharmaceutical composition.

Blocks 468-478. Referring to block 468 of FIG. 4E, the process controlproceeds to the fulfillment process when no filter 216 in the firstplurality of filters has been fired and the subject has acknowledgedeach warning 226 associated with each filter 222 in the second pluralityof filters that was fired. In some embodiments, the fulfillment processincludes storing an indication in a user profile 234 of an initial orderdate and/or destination for the PDE₅ inhibitor pharmaceuticalcomposition. The initial order date is utilized, for example, to verifyat least a refill status of a provision of the PDE₅ inhibitor. Theinitial order date is also utilized, for example, to verify at least anelapsed period of time between an initial order and a future re-order.Such verification is required in order to ensure that certain tests(e.g., blood pressure tests) are taken regularly.

The fulfillment process further includes communicating anover-the-counter drug facts label 230 for the PDE₅ inhibitorpharmaceutical composition to the subject. In some embodiments, the drugfacts label is communicated to the subject in real-time, e.g., withinthe same user interface as used for the qualification process. In someembodiments, the over-the-counter drug facts label 230 specifies whatthe PDE₅ inhibitor is for (e.g., to treat erectile dysfunction etc.),what dosage the subject is being authorized to take, and/or and anyrisks associated with taking PDE₅ inhibitor pharmaceutical composition(e.g., drug-drug interactions, pharmacokinetic interactions, adversereactions, etc.).

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label 230 has been received and read, the subjectis authorized for provision of a dosage of from 2.5 mg to 20 mg oftadalafil no more than once per day. In some embodiments, uponconfirmation from the subject that the over the counter drug facts label230 has been received and read, the subject is authorized for provisionof a dosage of from 2.5 mg to 10 mg of tadalafil no more than once perday (block 472). In some embodiments, upon confirmation from the subjectthat the over the counter drug facts label 230 has been received andread, the subject is authorized for provision of a dosage of from 5 mgto 20 mg of tadalafil no more than once per day. In some embodiments,upon confirmation from the subject that the over the counter drug factslabel 230 has been received and read, the subject is authorized forprovision of a dosage of 2.5 mg of tadalafil no more than once per day.In some embodiments, upon confirmation from the subject that the overthe counter drug facts label 230 has been received and read, the subjectis authorized for provision of a dosage of 5 mg of tadalafil no morethan once per day (block 474). In some embodiments, upon confirmationfrom the subject that the over the counter drug facts label 230 has beenreceived and read, the subject is authorized for provision of a dosageof 10 mg of tadalafil no more than once per day. In some embodiments,upon confirmation from the subject that the over the counter drug factslabel 230 has been received and read, the subject is authorized forprovision of a dosage of 20 mg of tadalafil no more than once per day.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label 230 has been received and read, the subjectis authorized for provision of a dosage of from 2.5 mg to 20 mg ofvardenafil no more than once per day. In some embodiments, uponconfirmation from the subject that the over the counter drug facts label230 has been received and read, the subject is authorized for provisionof a dosage of from 2.5 mg to 10 mg of vardenafil no more than once perday. In some embodiments, upon confirmation from the subject that theover the counter drug facts label 230 has been received and read, thesubject is authorized for provision of a dosage of from 5 mg to 20 mg ofvardenafil no more than once per day. In some embodiments, uponconfirmation from the subject that the over the counter drug facts label230 has been received and read, the subject is authorized for provisionof a dosage of 2.5 mg of vardenafil no more than once per day. In someembodiments, upon confirmation from the subject that the over thecounter drug facts label 230 has been received and read, the subject isauthorized for provision of a dosage of 5 mg of vardenafil no more thanonce per day. In some embodiments, upon confirmation from the subjectthat the over the counter drug facts label 230 has been received andread, the subject is authorized for provision of a dosage of 10 mg ofvardenafil no more than once per day. In some embodiments, uponconfirmation from the subject that the over the counter drug facts label230 has been received and read, the subject is authorized for provisionof a dosage of 20 mg of vardenafil no more than once per day.

Referring to blocks 476 and 478, in some embodiments the fulfillmentprocess further includes authorizing provision of the PDE₅ inhibitorpharmaceutical composition to the subject. The authorization occurs uponconfirmation from the subject that the over-the-counter drug facts label230 has been received and read by the subject. In some embodiments, thisauthorization includes a destination associated with the subject. Insome embodiments, the destination associated with the subject is storedin the user profile 234 (block 476). In some embodiments, thedestination associated with the subject is a physical address includinga street address, a Post Office box, a pharmacy associated with thesubject, a health care provider associated with the subject, and/or oneor more coordinates (e.g., longitude, latitude, elevation). In someembodiments, the provision of the PDE₅ inhibitor pharmaceuticalcomposition to the subject comprises shipping the PDE₅ inhibitorpharmaceutical composition to the physical address associated with thesubject (block 478). In some embodiments, the provision of the PDE₅inhibitor pharmaceutical composition to the subject comprises shippingthe PDE₅ inhibitor pharmaceutical composition to a pharmacy associatedand/or a location associated with a health care provider of the subjectand/or an office of a medical practitioner associated with the subject.

Blocks 480-514. Referring to blocks 480-514 of FIGS. 4F-4I, are-fulfillment process will be described infra. In some embodiments, thepresent disclosure provides a method for qualifying a subject for arefill of a PDE₅ inhibitor pharmaceutical composition. In someembodiments, the qualification for a refill of the PDE₅ inhibitorpharmaceutical composition follows an initial qualification of thesubject, as described herein. In some embodiments, the qualification fora refill of the PDE₅ inhibitor pharmaceutical composition followsissuance of a prescription to the subject for the PDE₅ inhibitorpharmaceutical composition. For example, in some embodiments, a subjectwho is new to the qualification process is asked whether they previouslyreceived a prescription for the PDE₅ inhibitor pharmaceuticalcomposition and, if the subject indicates that they have not previouslyreceived a prescription, the subject is directed to an initialqualification method and, if the subject indicates that they havepreviously received a prescription, the subject is directed to therefill qualification method, e.g., as described below.

Referring to block 480 of FIG. 4F, in some embodiments a re-fulfillmentprocedure is performed. The re-fulfillment procedure is responsive toreceiving a re-order request from the subject for the PDE₅ inhibitorpharmaceutical composition. In some embodiments, a prompt to initiatethe re-fulfillment procedure is sent to user device 102 associated withthe subject after a predetermined amount of time associated with aduration of dosages previously delivered to the subject (e.g., the useris reminded to fulfill their order of the PDE₅ inhibitor pharmaceuticalcomposition just before, or just after, the user is scheduled to run outof a previously delivered provision).

Referring to blocks 482-484, in some embodiments the re-fulfillmentprocedure includes conducting a second survey of the subject. The secondsurvey is configured to obtain a second plurality of survey results.These results are derived from corresponding survey questions (e.g., thedevice transmits one or more survey questions to the user, prompting aresponse, and then receives a response to the one or more surveyquestions back from the subject). In some embodiments, the secondplurality of survey results include, or at least indicate, some or allof the subject characteristics listed in Table 4. For example, in someembodiments, the second plurality of survey results includes, or atleast indicates, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, or all 18 of the characteristic listed in Table 4. In oneembodiment, the second survey questions and results include at leastcharacteristics 1-17 as provided in Table 4.

In some embodiments, the second survey results indicate at least one of:an erectile dysfunction status of the subject (e.g., responsive to asurvey question that is associated with and/or applied to (804) anerectile dysfunction filter 216-7 of a first category class 214-2),whether the subject has started to take a nitrate or nitrite vasodilatorcomposition since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition (e.g., responsive to a survey question thatis associated with and/or applied to (806, 808) a vasodilator filter216-8 of a first category class), whether the subject has started totake a guanylate cyclase stimulator medication since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition (e.g.,responsive to a survey question that is associated with and/or appliedto (810) a guanylate cyclase stimulator filter 216-9 of a first categoryclass), whether the subject has started to take a PDE₅ inhibitorcomposition since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition (e.g., responsive to a survey question thatis associated with and/or applied to (812) a PDE₅ inhibitor filter216-10 of a first category class), whether the subject has developedsymptoms of heart problems during sexual intercourse since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition(e.g., responsive to a survey question that is associated with and/orapplied to (814) a sexual intercourse filter 216-11 of a first categoryclass), whether the subject has experienced priapism since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition(e.g., responsive to a survey question that is associated with and/orapplied to (816) a priapism filter 216-12 of a first category class),whether the subject has developed hearing or vision loss since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition(e.g., responsive to a survey question that is associated with and/orapplied to (818,820) a sensory deterioration filter 216-13 of a firstcategory class), whether the subject has developed a symptom of heartproblems since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition (e.g., responsive to a survey question thatis associated with and/or applied to (822) a heart problem filter 222-14of a second category class 220-2), a blood pressure status of thesubject (e.g., responsive to a survey question that is associated withand/or applied to (824,826) a blood pressure filter 222-15 of a secondcategory class), whether the subject has had a stroke since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition(e.g., responsive to a survey question that is associated with and/orapplied to (828) a stroke filter 222-16 of a second category class),whether the subject has developed a liver problem since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition (e.g.,responsive to a survey question that is associated with and/or appliedto (830) a liver disease filter 222-17 of a second category class), akidney function status of the subject (e.g., responsive to a surveyquestion that is associated with and/or applied to (832) a kidneydisease filter 222-18 of a second category class), whether the subjecthas developed retinitis pigmentosa since receiving their last provisionof the PDE₅ inhibitor pharmaceutical composition (e.g., responsive to asurvey question that is associated with and/or applied to (834) aretinitis pigmentosa filter 222-19 of a second category class), whetherthe subject has developed a stomach ulcer since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition (e.g.,responsive to a survey question that is associated with and/or appliedto (836) a stomach ulcer filter 222-20 of a second category class),whether the subject has developed a bleeding disorder since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition(e.g., responsive to a survey question that is associated with and/orapplied to (838) a bleeding problem filter 222-21 of a second categoryclass), whether the subject has developed an abnormal genital shapesince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition (e.g., responsive to a survey question thatis associated with and/or applied to (840) a genital abnormality filter222-22 of a second category class), whether the subject has developed ablood cell disorder since receiving their last provision of the PDE₅inhibitor pharmaceutical composition (e.g., responsive to a surveyquestion that is associated with and/or applied to (842) a blood celldisorder filter 222-23 of a second category class), and whether thesubject has started taking a medication that interacts with the PDE₅inhibitor pharmaceutical composition since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition (e.g.,responsive to a survey question that is associated with and/or appliedto (844-854) a drug interaction filter 222-24 of a second categoryclass).

In some embodiments, the second survey includes questions that elicitresponses providing some or all of the characteristics listed in Table4. In some embodiments, the second survey includes questionscorresponding to each of the survey results required for the methodsdescribed herein. In other embodiments, the second survey includesquestions corresponding to only a subset of the survey results requiredfor the methods described herein. In some embodiments, other surveyresults required for the methods described herein are acquired throughother means (e.g., upon registration/subscription for a serviceassociated with qualifying the subject for over-the-counter medication,from a healthcare provider, from a prior survey, from a databaseassociated with a pharmacy, etc.) For example, in some embodiments, thesubject provides a personal medical identification associated with aninsurer, a hospital, or other healthcare provider and information aboutthe subject required for the methods described herein, e.g., one or moresurvey results, is acquired from a preexisting database associated withthe personal medical identification (e.g., a blood pressure measurementdetermined for the subject).

TABLE 4 Example characteristics for re-qualifying a subject for anover-the- counter provision of a PDE₅ inhibitor pharmaceuticalcomposition. Result Example Characteristics 1 an erectile dysfunctionstatus of the subject 2 whether the subject has started to take anitrate or nitrite vasodilator composition 3 whether the subject hasstarted to take a guanylate cyclase stimulator medication 4 whether thesubject has started to take a PDE₅ inhibitor composition 5 whether thesubject has developed symptoms of heart problems during sexualintercourse 6 whether the subject has experienced priapism 7 whether thesubject has developed hearing or vision loss 8 whether the subject hasdeveloped a symptom of heart problems 9 a blood pressure status of thesubject 10 whether the subject has had a stroke 11 whether the subjecthas developed a liver problem 12 a kidney function status of the subject13 whether the subject has developed retinitis pigmentosa 14 whether thesubject has developed a stomach ulcer 15 whether the subject hasdeveloped a bleeding disorder 16 whether the subject has developed anabnormal genital shape 17 whether the subject has developed a blood celldisorder since 18 whether the subject has started taking a medicationthat interacts with the PDE₅

It is contemplated that, in some embodiments, any one or more of thesurvey questions provided in Table 4 will not be included in the secondsurvey (e.g., will not be used for the reassessment). For example, insome embodiments, a characteristic associated with a particular surveyquestions will be informative when qualifying a subject for oneparticular PDE₅ inhibitor but not for another PDE₅ inhibitor. Forinstance, a survey question is queried for tadalafil qualifying surveysbut not for vardenafil qualifying surveys. The skilled artisan willrecognize that different PDE₅ inhibitor carry different risk and druginteraction profiles. Accordingly, survey information required forqualifying a subject for access to one PDE₅ inhibitor with a knownadverse drug interaction may not be necessary for qualifying the samesubject for access to a second PDE₅ inhibitor.

Accordingly, it is contemplated that the second survey questions elicitresponses to any sub-set of survey results provided in Table 4. Forbrevity, all possible combinations of the characteristics provided inTable 4 are not specifically delineated here. However, the skilledartisan will easily be able to envision any particular subset of surveyquestions designed to elicit responses to any subset of characteristicsprovided in Table 4. Likewise, the skilled artisan may know of othersurvey questions, not provided in Table 4, that may be combined with anysubset of the survey questions provided in Table 4 to form the secondsurvey questions used in the methods described herein.

Referring to block 486 of FIG. 4G, all or a portion the results are runagainst a third plurality of filters of the first category class. When arespective filter in the third plurality of filters is fired (e.g., whena survey result indicates that a triggering condition 218 has been met),the subject is deemed not qualified for the PDE₅ inhibitorpharmaceutical composition and the method is terminated without deliveryof the PDE₅ inhibitor pharmaceutical composition.

Referring to blocks 488-500, specific filters in the third plurality offilters and their exemplary triggering conditions that cause thecorresponding filter to fire are detailed.

In some embodiments, the third plurality of filters of the firstcategory class 214 includes some or all of the filters 216 listed inTable 5. For example, in some embodiments, the first plurality offilters results includes 2, 3, 4, 5, 6, or all 7 of the filters listedin Table 5. In one embodiment, the third plurality of filters includesall of filters 1-7 as provided in Table 5.

TABLE 5 Example filters for contraindications associated with re-qualification of a subject for an over-the-counter provision of a PDE₅inhibitor pharmaceutical composition. Filter Example Criteria 1a anerectile dysfunction filter 2a a vasodilator filter 3a a guanylatefilter 4a a PDE₅ inhibitor filter 5a a sexual intercourse filter 6a apriapism filter 7a a sensory deterioration filter

It is contemplated that, in some embodiments, any one or more of thefilters provided in Table 5 will not be included in the third pluralityof filters. For example, in some embodiments, a characteristicassociated with a particular survey result will be informative whenqualifying a subject for one particular PDE₅ inhibitor but not foranother PDE₅ inhibitor. Likewise, the skilled artisan may know of otherfilters, not provided in Table 5, which may be combined with any subsetof the filters provided in Table 5 to form the third plurality offilters results used in the methods described herein. For brevity, allpossible combinations of the filters provided in Table 5 are notspecifically delineated here.

Referring to block 488, in some embodiments the third plurality offilters includes an erectile dysfunction filter, e.g., as describedabove in relation to the first survey. In some embodiments, the erectiledysfunction filter is configured to be fired at least when the secondplurality of survey results indicates that the subject does not haveerectile dysfunction. When the erectile dysfunction filter is fired, thesubject is not permitted to obtain the PDE₅ inhibitor pharmaceuticalcomposition over-the-counter (e.g., the method is terminated withoutauthorizing re-provision of the PDE₅ inhibitor pharmaceuticalcomposition to the subject). In some embodiments, the second pluralityof survey results indicates that the subject does not have erectiledysfunction when the survey results indicate that the subject did nothave erectile dysfunction since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition. For instance, in someembodiments a subject does not have erectile dysfunction but is stillrecommended to obtain a PDE₅ inhibitor composition.

Referring to block 490, in some embodiments the third plurality offilters includes a vasodilator filter, e.g., as described above inrelation to the first survey. In some embodiments, the vasodilatorfilter is configured to be fired at least when the second plurality ofsurvey results indicates that the subject has been taking a vasodilatorcomposition including a nitrate or a nitrite (e.g., nitroglycerin, alkylnitrite, amyl nitrate, amyl nitrite, butyl nitrite, etc.) When thevasodilator filter is fired, the subject is not permitted to obtain thePDE₅ inhibitor pharmaceutical composition over-the-counter (e.g., themethod is terminated without authorizing re-provision of the PDE₅inhibitor pharmaceutical composition to the subject). In someembodiments, the second plurality of survey results indicates that thesubject is taking a vasodilator composition comprising a nitrate or anitrite when the survey results indicate that the subject was taking avasodilator composition comprising a nitrate or a nitrite sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 492, in some embodiments the third plurality offilters includes a guanylate cyclase stimulator filter, e.g., asdescribed above in relation to the first survey. In some embodiments,the guanylate cyclase stimulator filter is configured to be fired atleast when the second plurality of survey results indicates that thesubject is taking a guanylate cyclase stimulator mediation. When theguanylate cyclase stimulator filter is fired, the subject is notpermitted to obtain the PDE₅ inhibitor pharmaceutical compositionover-the-counter (e.g., the method is terminated without authorizingre-provision of the PDE₅ inhibitor pharmaceutical composition to thesubject). In some embodiments, the second plurality of survey resultsindicates that the subject is taking a guanylate cyclase stimulatormediation when the survey results indicate that the subject was taking aguanylate cyclase stimulator mediation since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition.

Referring to block 494, in some embodiments the third plurality offilters includes a PDE₅ inhibitor filter, e.g., as described above inrelation to the first survey. In some embodiments, the PDE₅ inhibitorfilter is configured to be fired at least when the second plurality ofsurvey results indicates that the subject is taking a PDE₅ inhibitorcomposition. When the PDE₅ inhibitor filter is fired, the subject is notpermitted to obtain the PDE₅ inhibitor pharmaceutical compositionover-the-counter (e.g., the method is terminated without authorizingre-provision of the PDE₅ inhibitor pharmaceutical composition to thesubject). In some embodiments, the second plurality of survey resultsindicates that the subject is taking a PDE₅ inhibitor composition whenthe survey results indicate that the subject is taking a PDE₅ inhibitorcomposition since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition.

Referring to block 496, in some embodiments the third plurality offilters includes a sexual intercourse filter. In some embodiments, thesexual intercourse filter is configured to be fired at least when thesecond plurality of survey results indicates that the subject hasdeveloped symptoms of heart problems during sexual intercourse sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. When the sexual intercourse filter is fired, the subject isnot permitted to obtain the PDE₅ inhibitor pharmaceutical compositionover-the-counter (e.g., the method is terminated without authorizingre-provision of the PDE₅ inhibitor pharmaceutical composition to thesubject). In some embodiments, the second plurality of survey resultsindicates that the subject has developed symptoms of heart problemsduring intercourse when the second plurality of survey results indicatethat the subject has been diagnosed symptoms of heart problems duringintercourse since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed symptoms ofheart problems during sexual intercourse when the second plurality ofsurvey results indicate that the subject has been diagnosed withsymptoms of heart problems during sexual intercourse since receivingtheir last provision of the PDE₅ inhibitor composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed symptoms of heart problems during sexualintercourse when the second plurality of survey results indicate thatthe subject has experienced a symptom (e.g., a new and/or worseningsymptom) of heart problems since receiving their last provision of thePDE₅ inhibitor composition, e.g., angina pectoris, AV block, migraines,syncope, tachycardia, palpitations, hypotension, postural hypotension,myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure,abnormal electrocardiogram, and/or cardiomyopathy.

Referring to block 498, in some embodiments the third plurality offilters includes a priapism filter (e.g., as described above in relationto the first survey). In some embodiments, the priapism filter isconfigured to be fired at least when the second plurality of surveyresults indicates that the subject has had priapism since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition.When the priapism filter is fired, the subject is not permitted toobtain the PDE₅ inhibitor pharmaceutical composition over-the-counter(e.g., the method is terminated without authorizing re-provision of thePDE₅ inhibitor pharmaceutical composition to the subject). In someembodiments, the second plurality of survey results indicates that thesubject has had priapism when the survey results indicate that thesubject had priapism since receiving their last provision of the PDE5inhibitor pharmaceutical composition. In some embodiments, the secondplurality of survey results indicates that the subject has experiencedpriapism when the second plurality of survey results indicate that thesubject has been diagnosed with priapism since receiving their lastprovision of the PDE5 inhibitor composition. In some embodiments, thesecond plurality of survey results indicates that the subject hasexperienced priapism when the second plurality of survey resultsindicate that the subject has experienced a symptom (e.g., a new and/orworsening symptom) of priapism since receiving their last provision ofthe PDE5 inhibitor composition, e.g., an erection lasting four hours orgreater.

Referring to block 500, in some embodiments the third plurality offilters includes a sensory deterioration filter. In some embodiments,the sensory deterioration filter is configured to be fired at least whenthe second plurality of survey results indicates that the subject hasdeveloped sudden vision loss and/or a sudden hearing loss sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. In some embodiments, the second plurality of survey resultsindicates that the subject has developed sensory deterioration when thesecond plurality of survey results indicate that the subject has beendiagnosed with sensory deterioration since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed sensory deterioration when the second plurality ofsurvey results indicate that the subject has experienced (e.g., a newand/or worsening symptom) sensory deterioration since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition thesensory deterioration filter is configured to be fired at least when thesecond plurality of survey results indicates that the subject hasdeveloped tinnitus, vertigo, and/or dizziness. When the sensorydeterioration filter is fired, the subject is not permitted to obtainthe PDE₅ inhibitor pharmaceutical composition over-the-counter (e.g.,the method is terminated without authorizing re-provision of the PDE₅inhibitor pharmaceutical composition to the subject).

In some embodiments, the device accounts for gaps in the subject's useof the PDE₅ inhibitor pharmaceutical composition when determiningwhether the subject's erectile dysfunction is being effectively managedby administration of the composition (e.g., in some embodiments, wherethe device determines that the user has been without a provision of thePDE₅ pharmaceutical composition for a threshold period of time, thedevice bypasses the blood pressure filter, or relaxes the requirementsof the filter, for example, to a blood pressure level below that of thestandard blood pressure levels required to trigger the blood pressurefilter).

Referring to block 502 of FIG. 4H, the method also includes running allor a portion of the second survey results against a fourth plurality offilters of the second category class 220-2. When a respective filter inthe fourth plurality of filters is fired, the subject is provided with awarning corresponding to the respective filter. In some embodiments, thewarning is provided as a next step, e.g., prior to applying surveyresults to any subsequent filters, after the corresponding filter isfired. For example, with respect to FIG. 8A, in some embodiments, e.g.,when the erectile dysfunction filter is triggered at 804, the devicewould provide the subject with a warning prior to proceeding to thevasodilator filter at 804, e.g., requiring the subject confirm they havediscussed their erectile dysfunction with a health care provider and thehealthcare provider still recommends taking a PDE₅ inhibitorpharmaceutical composition. In some embodiments the warning is providedafter applying survey results to all subsequent filters. For example,with respect to FIGS. 8A and 8E, in some embodiments, e.g., when theerectile dysfunction filter is triggered at 804, the device wouldproceed to the vasodilator filter at 806 prior to transmitting a warningto the subject, and then transmit all warnings corresponding to filtersof the second category class, at 856, after survey results have beenapplied to all subsequent filters.

In some embodiments, the fourth plurality of filters of the secondcategory class 220-2 includes some or all of the filters listed in Table6. For example, in some embodiments, the fourth plurality of filtersincludes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or all 12 of the filters listedin Table 6. In some embodiments, the fourth plurality of filters of thesecond category class includes at least filters 1-11 as listed in Table6.

TABLE 6 Example filters for risk factors associated with re- qualifyinga subject for an over-the-counter provision of a PDE5 inhibitorpharmaceutical composition Filter Exemplary Criteria 1a a heart problemfilter 2a a blood pressure filter 3a a stroke filter 4a a liver diseasefilter 5a a kidney disease filter 6a a retinitis pigmentosa filter 7a astomach ulcer filter 8a a bleeding problem filter 9a a genitalabnormality filter 10a  a blood cell disorder filter 11a  a druginteraction filter 12a  a side effects filter

It is contemplated that, in some embodiments, any one or more of thefilters provided in Table 6 will not be included in the fourth pluralityof filters. For example, in some embodiments, a characteristicassociated with a particular survey result will be informative whenqualifying a subject for one particular PDE₅ inhibitor pharmaceuticalcomposition but not for another PDE₅ inhibitor pharmaceuticalcomposition. Accordingly, it is contemplated that the fourth pluralityof filters includes any sub-set of filters provided in Table 6.Likewise, the skilled artisan may know of other filters, not provided inTable 6, that may be combined with any subset of the filters 222provided in Table 6 to form the fourth plurality of filters results usedin the methods described herein.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a heart problem filter (e.g., heart problem filter222-14 in FIG. 3 and/or filter 1a in Table 6). The heart problem filteris configured to be fired at least when the second plurality of surveyresults indicate that the subject has developed a heart problem sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. In some embodiments, the second plurality of survey resultsindicates that the subject has developed a heart problem when the secondplurality of survey results indicate that the subject has been diagnosedwith a heart problem since receiving their last provision of the PDE₅inhibitor pharmaceutical composition. In some embodiments, the secondplurality of survey results indicates that the subject has developed aheart problem when the second plurality of survey results indicate thatthe subject has experienced a symptom (e.g., a new and/or worseningsymptom) of a heart problem since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, e.g., a heart attack, a heartfailure, irregular heartbeats, arrhythmia, angina, chest pain, and/ornarrowing of the aortic valve (block 436). When the heart problem filteris fired, the device transmits a warning corresponding to the heartproblem filter, and requires the user to acknowledge the warning beforeauthorizing a provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a blood pressure filter (e.g., blood pressure filter222-15 in FIG. 3 and/or filter 2a in Table 3). The blood pressure filteris configured to be fired at least when the second plurality of surveyresults indicates that the subject has either low blood pressure oruncontrolled high blood pressure. In some embodiments, the bloodpressure filter is configured to be fired at least when the secondplurality of survey results indicates that the subject has pulmonaryhypertension. In some embodiments, the blood pressure filter comprises afirst filter that is configured to be fired when the second plurality ofsurvey results indicates that the subject has either low blood pressureor uncontrolled high blood pressure and a second filter that isconfigured to be fired when the second plurality of survey resultsindicates that the subject has pulmonary hypertension. In someembodiments, a blood pressure cutoffs defining when the blood pressurefilter is fired and when the blood pressure filter is not fired are setaccording to a set of healthcare guidelines, which may change over time,and/or vary on a jurisdiction-by-jurisdiction basis. For example, in theUnited States, the American College of Cardiology and the American HeartAssociation collaborated to provide guidance on management of high bloodpressure. Whelton P K, et al., J Am Coll Cardiol., S0735-1097(17)41519-1(2017), the contents of which are hereby expressly incorporated byreference. These guidelines change over time as medical research andadvances in treatment better inform management of high and low bloodpressure. When the blood pressure filter is fired, the device transmitsa warning corresponding to the blood pressure filter, and requires theuser to acknowledge the warning before authorizing a provision of thePDE₅ inhibitor pharmaceutical composition. In some embodiments, thesecond plurality of survey results indicates that the subject haspulmonary hypertension when the second plurality of survey resultsindicate that the subject had pulmonary hypertension since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition.In some embodiments, the second plurality of survey results indicatesthat the subject has developed pulmonary hypertension when the secondplurality of survey results indicate that the subject has been diagnosedwith pulmonary hypertension since receiving their last provision of thePDE₅ inhibitor composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed pulmonaryhypertension when the second plurality of survey results indicate thatthe subject has experienced a symptom (e.g., a new and/or worseningsymptom) of pulmonary hypertension since receiving their last provisionof the PDE₅ inhibitor composition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a stroke filter (e.g., stroke filter 222-16 in FIG. 3and/or filter 3a in Table 3). The stroke filter is configured to befired at least when the second plurality of survey results indicatesthat the subject has had a stroke. When the stroke filter is fired, thedevice transmits a warning corresponding to the stroke filter, andrequires the user to acknowledge the warning before authorizing aprovision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has had a stroke when the second plurality of survey resultsindicate that the subject had a stroke since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a liver disease filter. The liver disease filter isconfigured to be fired at least when the second plurality of surveyresults indicates that the subject has developed a liver disease or aliver problem since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed a liver diseaseor a liver problem when the second plurality of survey results indicatethat the subject has been diagnosed with a liver disease or a liverproblem since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed a liver diseaseor a liver problem when the second plurality of survey results indicatethat the subject has experienced a symptom (e.g., a new and/or worseningsymptom) of a liver disease or a liver problem since receiving theirlast provision of the PDE5 inhibitor pharmaceutical composition, e.g.,impaired hepatic function, acute liver failure, and cholestasis. In someembodiments, the liver disease filter is fired at least when the secondplurality of survey results indicates that the subject has had areduction in liver function since receiving their last provision of thePDE5 inhibitor pharmaceutical composition. When the liver disease filteris fired, the device transmits a warning corresponding to the liverdisease filter, and requires the user to acknowledge the warning beforeauthorizing a provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a kidney disease filter. The kidney disease filter isconfigured to be fired at least when the second plurality of surveyresults indicates that the subject has developed a kidney problem sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. When the kidney disease filter is fired, the devicetransmits a warning corresponding to the kidney disease filter, andrequires the user to acknowledge the warning before authorizing aprovision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed a kidney problem when the second plurality ofsurvey results indicate that the subject has developed a kidney problemsince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed a kidney problemwhen the second plurality of survey results indicate that the subjecthas been diagnosed with a kidney problem since receiving their lastprovision of the PDE₅ inhibitor composition. In some embodiments, thesecond plurality of survey results indicates that the subject hasdeveloped a kidney problem when the second plurality of survey resultsindicate that the subject has experienced a symptom (e.g., a new and/orworsening symptom) of a kidney problem since receiving their lastprovision of the PDE₅ inhibitor composition e.g., fatigue, high bloodpressure, loss of appetite, malaise, and/or water-electrolyte imbalance.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a retinitis pigmentosa filter. The retinitis pigmentosafilter is configured to be fired at least when the second plurality ofsurvey results indicates that the subject has been diagnosed withretinitis pigmentosa since receiving their last provision of the PDE₅inhibitor pharmaceutical composition. When the retinitis pigmentosafilter is fired, the device transmits a warning corresponding to theretinitis pigmentosa filter, and requires the user to acknowledge thewarning before authorizing a provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has been diagnosed withretinitis pigmentosa when the second plurality of survey resultsindicate that the subject was diagnosed with retinitis pigmentosareceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a stomach ulcer filter. The stomach ulcer filter isconfigured to be fired at least when the second plurality of surveyresults indicates that the subject has developed a stomach ulcer sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. When the stomach ulcer filter is fired, the devicetransmits a warning corresponding to the stomach ulcer filter, andrequires the user to acknowledge the warning before authorizing aprovision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed a stomach ulcer when the second plurality ofsurvey results indicate that the subject was diagnosed with a stomachulcer receiving their last provision of the PDE₅ inhibitorpharmaceutical composition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a bleeding problem filter. The bleeding problem filteris configured to be fired at least when the second plurality of surveyresults indicates that the subject has developed a bleeding disordersince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, bleeding disordersindicate significant active peptic ulceration. When the bleeding problemfilter is fired, the device transmits a warning corresponding to thebleeding problem filter, and requires the user to acknowledge thewarning before authorizing a provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed a bleedingdisorder when the second plurality of survey results indicate that thesubject was diagnosed with a bleeding disorder since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed a bleeding problem when the second plurality ofsurvey results indicate that the subject has been diagnosed with ableeding problem since receiving their last provision of the PDE₅inhibitor composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed a bleedingproblem when the second plurality of survey results indicate that thesubject has experienced a symptom (e.g., a new and/or worsening symptom)of a bleeding problem since receiving their last provision of the PDE₅inhibitor composition e.g., a coagulation problem.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a genital abnormality filter. The genital abnormalityfilter is configured to be fired at least when the second plurality ofsurvey results indicates that the subject has developed an abnormalpenile shape since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, a condition which iscapable of firing the genital abnormality filter includes angulation,cavernosal fibrosis, or Peyronie's disease. When the genital abnormalityfilter is fired, the device transmits a warning corresponding to thegenital abnormality filter, and requires the user to acknowledge thewarning before authorizing a provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, the second plurality ofsurvey results indicates that the subject has developed an abnormalpenile shape when the second plurality of survey results indicate thatthe subject has developed an abnormal penile shape since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a blood cell disorder filter. The blood cell disorderfilter is configured to be fired at least when the second plurality ofsurvey results indicates that the subject has developed a blood disordersince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition. In some embodiments, blood cell disordersinclude sickle cell anemia, multiple myeloma, and leukemia. When theblood cell disorder filter is fired, the device transmits a warningcorresponding to the blood cell disorder filter, and requires the userto acknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition. In some embodiments, the secondplurality of survey results indicates that the subject has developed ablood disorder when the second plurality of survey results indicate thatthe subject has developed a blood disorder since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition. In someembodiments, the second plurality of survey results indicates that thesubject has developed a blood cell disorder when the second plurality ofsurvey results indicate that the subject has been diagnosed with a bloodcell disorder since receiving their last provision of the PDE₅ inhibitorcomposition. In some embodiments, the second plurality of survey resultsindicates that the subject has developed a blood cell disorder when thesecond plurality of survey results indicate that the subject hasexperienced a symptom (e.g., a new and/or worsening symptom) of a bloodcell disorder since receiving their last provision of the PDE₅ inhibitorcomposition.

Referring to block 504, in some embodiments, the fourth plurality offilters includes a drug interaction filter. The drug interaction filteris configured to be fired at least when the second plurality of surveyresults indicates that the subject indicates that the subject hasstarted taking a medication that interacts (e.g., a pharmacokineticinteraction and/or a pharmacodynamic interaction) with the PDE₅inhibitor pharmaceutical composition. In some embodiments, the druginteraction filter is fired when the second plurality of survey resultsindicates that the subject has started taking a medication selected fromthe group consisting of an alpha blocker (e.g., terazosin, tamsulosin,doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride and tamsulosinHCl, and silodosin), an HIV protease inhibitor (e.g., ritonavir), anantifungal medication (e.g., ketoconazole and itraconazole), anantibiotic (e.g., clarithromycin, telithromycin, and erythromycin), ablood pressure medication (e.g., a medication to treat hypertension),and an erectile dysfunction medication (block 462). When the druginteraction filter is fired, the device transmits a warningcorresponding to the drug interaction filter, and requires the user toacknowledge the warning before authorizing a provision of the PDE₅inhibitor pharmaceutical composition. As previously described, theseinteractions can be pharmacodynamic drug-drug interactions orpharmacokinetic drug-drug interactions. In some embodiments, theinteractions (e.g., triggering conditions 224) that are capable offiring the second drug interaction filter are the same as theinteractions that are capable of firing the first drug interactionfilter assuming that the PDE₅ inhibitor pharmaceutical composition isthe same between the fulfillment process and the re-fulfillment process.In some embodiments, the second plurality of survey results indicatesthat the subject has started taking a medication that interacts with thePDE₅ inhibitor pharmaceutical composition when the second plurality ofsurvey results indicate that the subject is taking a medication thatinteracts with the PDE₅ inhibitor since receiving their last provisionof the PDE₅ inhibitor pharmaceutical composition.

Referring to block 506, in some embodiments the second survey resultsfurther includes whether the subject has developed side effectsassociated with the PDE₅ inhibitor pharmaceutical composition sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition. Accordingly, in some embodiments, the fourth plurality offilters further comprises a side effect filter that is configured to befired at least when the second survey results indicate that the subjecthas developed side effects since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition. Side effects that are capableof triggering (e.g., triggering condition) the side effect filterindicate headaches, abnormal vision, muscle pain, nausea, dizziness, anda skin rash. In some embodiments, side effects that are capable oftriggering the side effect filter include a stuffy nose, a runny nose,back pain, and/or indigestion. When the side effect filter is fired, thedevice transmits a warning corresponding to the medical issue filter,and requires the user to acknowledge the warning before authorizing aprovision of the metformin pharmaceutical composition.

Referring to block 508, in some embodiments when a respective filter inthe third plurality of filters or fourth plurality of filters is fired,a record associated with the firing of the respective filter is stored(e.g., memorializing an adverse event that is required to be reported toa regulatory agency). This record is stored in an adverse event module242 which comprises records of filter firing events associated with aplurality of subjects (e.g., an aggregation of adverse events associatedwith the PDE₅ inhibitor pharmaceutical composition across a populationof subjects taking the PDE₅ inhibitor pharmaceutical compositionover-the-counter). In some embodiments, an indication the adverse eventis communicated to a third party (e.g., a medical practitionerassociated with the subject, a health care provider of the subject, amanufacturer/promoter of the PDE₅ inhibitor pharmaceutical composition,and/or a regulatory agency). In some embodiments, the indication isautomatically stored in the adverse event module 242 when a responsesubmitted by a subject as part of the second survey, triggers a filterassociated with an adverse event.

Referring to block 510, in some embodiments the method also includesobtaining acknowledgment from the subject for each warning issued to thesubject by any filter in the fourth plurality of filters. As describedwith respect to the warnings issued in conjunction with the secondplurality of filters of the second category class, in some embodiments,the warning includes a prompt for the subject to indicate whether theyhave discussed the risk factor underlying the respective filter in thesecond plurality of filters that was fired with a health carepractitioner (e.g., a licensed medical practitioner), e.g., and thehealth care practitioner indicated that the subject should take a PDE₅inhibitor pharmaceutical composition in view of the underlying riskfactor. Accordingly, acknowledgement is obtained from the subject whenthe subject indicates that they have discussed the risk factorunderlying the respective filter in the fourth plurality of filters thatwas fired with a health care provider.

Referring to block 512 of FIG. 4I, in some embodiments the procedurefurther includes proceeding with the re-fulfillment process when there-fulfillment process is not already terminated by the firing of afilter in the third plurality of filters (e.g., the second erectiledysfunction filter). In order for completion of the re-fulfillmentprocess, the subject is required to acknowledge each warning associatedwith each filter 22 in the fourth plurality of filters that was fired.

Referring to block 514, in some embodiments the re-fulfillment processalso includes storing a record in the user profile 234 of the subject ofa re-order 238 for the PDE₅ inhibitor pharmaceutical composition.

The re-fulfillment process also includes communicating anover-the-counter drug facts label 230 for the PDE₅ inhibitorpharmaceutical composition to the subject. As previously described,communication of the over-the-counter drug facts label 230 can occur ina variety of means. Upon confirmation from the subject that theover-the-counter drug facts label 230 has been received and read, themethod includes authorizing a re-order provision of the PDE₅ inhibitorpharmaceutical composition to the subject. In some embodiments, thisre-order provision includes the destination of the subject.

FIG. 7 illustrates an example method (700) (e.g., performed at anelectric device) for qualifying a subject for an over-the-counter PDE₅inhibitor pharmaceutical composition. In some embodiments, the method ofFIG. 7 is utilized when the subject has not been previously qualifiedfor the PDE₅ inhibitor pharmaceutical composition. In some embodiments,the method of FIG. 7 is utilized when the subject was previouslyqualified for the PDE₅ inhibitor composition but a predetermined periodof time elapsed since the previous qualification/re-qualificationoccurred (e.g., the most recent qualification of the subject was greaterthan one year ago).

Referring to FIG. 7 , the device prompts (702) the subject toacknowledge a privacy notice. Since the present disclosure requires thesubject to know and input sensitive medical information (e.g.,information only the subject and a medical practitioner have access to),privacy of this information is important. Once the subject hasacknowledged they have the requisite privacy for continuing, the deviceproceeds with the qualification process.

The device prompts the subject to provide information about their genderand then applies (704) the answer received from the subject to a genderfilter. When the gender filter is fired (e.g., when the answer indicatesthe subject is not male), the device terminates (701) the qualificationprocess without authorizing provision of the PDE₅ inhibitorpharmaceutical agent and, optionally, transmits advice to the user as towhy they should not take the PDE₅ inhibitor pharmaceutical agent.

When the gender filter is not fired, the device proceeds with thequalification process, prompting the subject to provide informationindicating their age and then applies (706) the answer received from thesubject to an age filter. When the age filter is fired (e.g., when theanswer indicates the subject is younger than eighteen years old), thedevice terminates (701) the qualification process without authorizingprovision of the PDE₅ inhibitor pharmaceutical agent and, optionally,transmits advice to the user as to why they should not take the PDE₅inhibitor pharmaceutical agent and/or to return once they have obtainedan age at which it would be appropriate to take a PDE₅ inhibitorpharmaceutical agent.

When the age filter is not fired, the device proceeds with thequalification process, prompting to provide information indicatingwhether the subject has erectile dysfunction and then applies (708) theanswer received from the subject to an erectile dysfunction filter. Whenthe erectile dysfunction filter is fired (e.g., when the answerindicates the subject does not have erectile dysfunction), the deviceterminates (701) the qualification process without authorizing provisionof the PDE₅ inhibitor pharmaceutical agent and, optionally, transmitsadvice to the user as to why they should not take the PDE₅ inhibitorpharmaceutical agent.

When the erectile dysfunction filter is not fired, the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject is taking a nitrate ornitrite vasodilator composition and then applies (710) the answerreceived from the subject to a vasodilator filter. When the vasodilatorfilter is fired (e.g., when the answer indicates the subject is taking anitrate or nitrite vasodilator), the device terminates (701) thequalification process without authorizing provision of the PDE₅inhibitor pharmaceutical agent and, optionally, transmits advice to theuser as to why they should not take the PDE₅ inhibitor pharmaceuticalagent.

When the vasodilator filter is not fired, the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject is taking a guanylate cyclase stimulatormedication and then applies (712) the answer received from the subjectto a guanylate cyclase stimulator filter. When the guanylate cyclasestimulator filter is fired (e.g., when the answer indicates the subjectis taking a guanylate cyclase stimulator composition), the deviceterminates (701) the qualification process without authorizing provisionof the PDE₅ inhibitor pharmaceutical agent and, optionally, transmitsadvice to the user as to why they should not take the PDE₅ inhibitorpharmaceutical agent

When the guanylate cyclase stimulator filter is not fired, the deviceproceeds with the qualification process, prompting the subject toprovide information indicating whether the subject is taking a PDE₅inhibitor composition and then applies (714) the answer received fromthe subject to a PDE₅ inhibitor filter. When the PDE₅ inhibitor filteris fired (e.g., when the answer indicates the subject is taking a PDE₅inhibitor composition), the device terminates (701) the qualificationprocess without authorizing provision of the PDE₅ inhibitorpharmaceutical agent and, optionally, transmits advice to the user as towhy they should not take the PDE₅ inhibitor pharmaceutical agent.

When the PDE₅ inhibitor filter is not fired, the device proceeds withthe qualification process, prompting the subject to provide informationindicating whether the subject has ever had a heart problem and thenapplies (716) the answer received from the subject to a heart problemfilter. When the heart problem filter is fired (e.g., when the answerindicates that the subject has been diagnosed with a heart problem) thedevice initiates (711-1) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). Whenthe heart problem filter is not fired (e.g., when the answer indicatesthe subject has not had a heart problem), the device proceeds with thequalification process, prompting the subject to provide informationindicating a pulmonary hypertension status and then applies (718) theanswer received from the subject to a pulmonary hypertension filter.When the pulmonary hypertension filter is fired (e.g., when the answerindicates that the subject has been diagnosed with pulmonaryhypertension) the device initiates (711-2) an override procedure (e.g.,creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with aheath care provider). When the pulmonary hypertension filter is notfired, the device proceeds with the qualification process, prompting thesubject to provide information indicating a blood pressure status andthen applies (720) the answer received from the subject to a bloodpressure filter. As previously described, in some embodiments, thepulmonary hypertension filter and the blood pressure filter are combinedas a single filter. When the blood pressure filter is fired (e.g., whenthe answer indicates that the subject has high blood pressure) thedevice initiates (711-3) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). Whenthe blood pressure problem filter is not fired (e.g., when the answerindicates the subject has normal blood pressure or controlled high bloodpressure), the device proceeds with the qualification process, promptingthe subject to provide information indicating whether the subject hasever had a stroke and then applies (722) the answer received from thesubject to a stroke filter. When the stroke filter is fired (e.g., whenthe answer indicates that the subject has had a stroke) the deviceinitiates (711-4) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). Whenthe stroke filter is not fired (e.g., when the answer indicates thesubject has not had a stroke), the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject has a liver problem and then applies(724) the answer received from the subject to a liver disease filter.When the liver disease filter is fired (e.g., when the answer indicatesthat the subject has been diagnosed with a liver problem) the deviceinitiates (711-1) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). Whenthe liver disease filter is not fired (e.g., when the answer indicatesthe subject does not have a liver problem), the device proceeds with thequalification process, prompting the subject to provide informationindicating a kidney function status of the subject and then applies(726) the answer received from the subject to a kidney disease filter.When the kidney disease filter is fired (e.g., when the answer indicatesthat the subject has been diagnosed with a kidney problem) the deviceinitiates (711-6) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). Whenthe kidney disease filter is not fired (e.g., when the answer indicatesthe subject does not have a kidney problem), the device proceeds withthe qualification process, prompting the subject to provide informationindicating whether the subject has retinitis pigmentosa and then applies(728) the answer received from the subject to a retinitis pigmentosafilter. When the retinitis pigmentosa filter is fired (e.g., when theanswer indicates that the subject has been diagnosed with retinitispigmentosa) the device initiates (711-7) an override procedure (e.g.,creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with aheath care provider). When the retinitis pigmentosa filter is not fired(e.g., when the answer indicates the subject does not have retinitispigmentosa), the device proceeds with the qualification process,prompting the subject to provide information indicating whether thesubject has developed vision loss and then applies (730) the answerreceived from the subject to a vision deterioration filter. When thevision deterioration filter is fired (e.g., when the answer indicatesthat the subject has experienced vision loss) the device initiates(711-8) an override procedure (e.g., creates a record indicating thatthe user must confirm they have discussed taking a PDE₅ inhibitorpharmaceutical composition with a heath care provider). When the visiondeterioration filter is not fired (e.g., when the answer indicates thesubject has not developed vision deterioration), the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has ever had a stomach ulcerand then applies (732) the answer received from the subject to a stomachulcer filter. When the stomach ulcer filter is fired (e.g., when theanswer indicates that the subject has developed a stomach ulcer) thedevice initiates (711-9) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a heath care provider). whenthe answer indicates the subject has not had a stomach ulcer), thedevice proceeds with the qualification process, prompting the subject toprovide information indicating whether the subject has a bleedingdisorder and then applies (734) the answer received from the subject toa bleeding disorder filter. When the bleeding disorder filter is fired(e.g., when the answer indicates that the subject has been diagnosedwith a bleeding disorder) the device initiates (711-10) an overrideprocedure (e.g., creates a record indicating that the user must confirmthey have discussed taking a PDE₅ inhibitor pharmaceutical compositionwith a heath care provider). When the bleeding disorder filter is notfired (e.g., when the answer indicates the subject has not had ableeding disorder), the device proceeds with the qualification process,prompting the subject to provide information indicating a genital statusof the subject and then applies (736) the answer received from thesubject to a genital abnormality filter. When the genital abnormalityfilter is fired (e.g., when the answer indicates that the subject has adeformed penis or Peyronie's disease) the device initiates (711-11) anoverride procedure (e.g., creates a record indicating that the user mustconfirm they have discussed taking a PDE₅ inhibitor pharmaceuticalcomposition with a heath care provider). When the genital abnormalityfilter is not fired (e.g., when the answer indicates the subject has anormal penile shape), the device proceeds with the qualificationprocess, prompting the subject to provide information indicating whetherthe subject has ever experienced priapism and then applies (738) theanswer received from the subject to a priapism filter. When the priapismfilter is fired (e.g., when the answer indicates that the subject hashad an erection lasting longer than four hours) the device initiates(711-12) an override procedure (e.g., creates a record indicating thatthe user must confirm they have discussed taking a PDE₅ inhibitorpharmaceutical composition with a heath care provider). When thepriapism filter is not fired (e.g., when the answer indicates thesubject has not experienced priapism), the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject has a blood cell disorder and thenapplies (740) the answer received from the subject to a blood celldisorder filter. When the blood cell disorder filter is fired (e.g.,when the answer indicates that the subject has been diagnosed with ablood cell disorder) the device initiates (711-13) an override procedure(e.g., creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with aheath care provider). When the blood cell disorder filter is not fired(e.g., when the answer indicates the subject does not have a blood celldisorder), the device proceeds with the qualification process.

The device then proceeds with the qualification process, prompting thesubject to provide information indicating whether the subject is takinga medication that interacts with the PDE₅ inhibitor pharmaceuticalcomposition and then applies (742-752) the answer received from thesubject to a drug interaction filter. In some embodiments, the druginteraction filter comprises a plurality of filters, where each filterin the plurality of filters is configured for a specific druginteraction. For instance, in some embodiments the drug interactionfilter comprises an alpha blocker filter, a hypertension medicationfilter, an HIV protease inhibitor filter, an oral antifungal filter, anantibiotics filter, and an erectile dysfunction medication filter. Whenthe drug interaction filter is fired (e.g., when the answer indicatesthe subject is taking a medication that interacts with the PDE₅inhibitor pharmaceutical composition), the device initiates(711-14-711-18) an override procedure (e.g., creates a record indicatingthat the user must confirm they have discussed taking a PDE₅ inhibitorpharmaceutical composition with a heath care provider).

The device proceeds with the qualification process, determining (753)whether the override procedure has been triggered (e.g., by firing ofone or more of the heart problem filter, the pulmonary hypertensionfilter, the blood pressure filter, the stroke filter, the liver diseasefilter, the kidney problem filter, the retinitis pigmentosa filter, thesensory deterioration filter, the stomach ulcer filter, the bleedingproblem filter, the genital abnormality filter, the priapism filter, orthe blood cell disorder filter, the alpha blocker filter, thehypertension medication filter, the HIV protease inhibitor filter, theoral antifungal filter, the antibiotics filter, and/or the erectiledysfunction medication filter). If the override procedure has beentriggered, the device prompts (717) the user to confirm that they havespoken with a medical professional about taking a PDE₅ inhibitorpharmaceutical composition (e.g., in view of the underlying risk factorthat triggered the heart problem filter, the pulmonary hypertensionfilter, the blood pressure filter, the stroke filter, the liver diseasefilter, the kidney problem filter, the retinitis pigmentosa filter, thesensory deterioration filter, the stomach ulcer filter, the bleedingproblem filter, the genital abnormality filter, the priapism filter, theblood cell disorder filter, the alpha blocker filter, the hypertensionmedication filter, the HIV protease inhibitor filter, the oralantifungal filter, the antibiotics filter, and/or the erectiledysfunction medication filter) and the medical professional recommendedtaking the PDE₅ inhibitor pharmaceutical composition. If the user'sresponse indicates they have not spoken with a medical professional orthe medical professional did not recommend taking the PDE₅ inhibitorpharmaceutical composition, the device terminates (703) the process and,optionally, transmits advice for the subject to consult a medicalprofessional.

If the override procedure was not triggered, or the override procedurewas triggered and the subject's response indicated that a medicalprofessional recommended they take a PDE₅ inhibitor pharmaceuticalcomposition (e.g., in view of the underlying risk factor triggering theoverride procedure), the device then proceeds with the qualificationprocess, prompting (754) the subject to confirm their answers. If theuser confirms their answers, the device transmits (831) a drug factslabel for the PDE₅ inhibitor pharmaceutical composition and prompts theuser to read the drug facts label. If the subject confirms they haveread the drug facts label, the device proceeds to authorize (758)purchase of the PDE₅ inhibitor pharmaceutical composition.

FIG. 8 illustrates an example method for qualifying a subject for arefill of an over-the-counter PDE₅ inhibitor pharmaceutical composition(e.g., following a prescription from a medical professional or initialqualification by a method described herein). Referring to FIG. 8 , thedevice prompts (802) the subject to acknowledge a privacy notice. Oncethe subject has acknowledged they have the requisite privacy forcontinuing, the device proceeds with the process, prompting the user toindicate their erectile dysfunction status and applies (804) the answerreceived from the subject to an erectile dysfunction filter. When theerectile dysfunction filter is fired (e.g., when the answer indicatesthe subject does not have erectile dysfunction), the device terminates(801) the qualification process, optionally transmitting advice to theuser as to why they should not take the PDE₅ inhibitor pharmaceuticalagent.

When the erectile dysfunction filter is not fired, the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has started to take a nitrateor nitrite vasodilator composition since receiving their last provisionof the PDE₅ inhibitor pharmaceutical composition and then applies (806)the answer received from the subject to a vasodilator filter. When thevasodilator filter is fired (e.g., when the answer indicates that thesubject is taking a vasodilator composition including a nitrate or anitrite), the device terminates (801) the qualification process withoutauthorizing provision of the PDE₅ inhibitor pharmaceutical agent and,optionally, transmits advice to the user as to why they should not takethe PDE₅ inhibitor pharmaceutical agent. When the vasodilator filter isnot fired, the device proceeds with the qualification process, promptingthe subject to provide information indicating whether the subject hasstarted to take a recreational drug known as “popper(s)” and thenapplies (808) the answer received from the subject to the vasodilatorfilter. As previously described, in some embodiments the prompts andprocesses (806,808) associated with the vasodilator filter are combinedinto a single prompt and process (807).

When the vasodilator filter is not fired, the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject has started to take a guanylate cyclasestimulator medication since receiving their last provision of the PDE₅inhibitor pharmaceutical composition and then applies (810) the answerreceived from the subject to a guanylate cyclase stimulator filter. Whenthe guanylate cyclase stimulator filter is fired (e.g., when the answerindicates the subject is taking a guanylate cyclase stimulatorcomposition), the device terminates (801) the qualification processwithout authorizing provision of the PDE₅ inhibitor pharmaceutical agentand, optionally, transmits advice to the user as to why they should nottake the PDE₅ inhibitor pharmaceutical agent.

When the guanylate cyclase stimulator filter is not fired, the deviceproceeds with the qualification process, prompting the subject toprovide information indicating whether the subject is taking a PDE₅inhibitor composition and then applies (812) the answer received fromthe subject to a PDE₅ inhibitor filter. When the PDE₅ inhibitor filteris fired (e.g., when the answer indicates the subject is taking a PDE₅inhibitor composition), the device terminates (801) the qualificationprocess without authorizing provision of the PDE₅ inhibitorpharmaceutical agent and, optionally, transmits advice to the user as towhy they should not take the PDE₅ inhibitor pharmaceutical agent.

When the PDE₅ inhibitor filter is not fired, the device proceeds withthe qualification process, prompting the subject to provide informationindicating whether the subject has developed symptoms of heart problemsduring sexual intercourse since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition and then applies (814) theanswer received from the subject to a sexual intercourse filter. Whenthe sexual intercourse inhibitor filter is fired (e.g., when the answerindicates the subject has developed symptoms of heart problems duringsexual intercourse since receiving their last provision of the PDE₅inhibitor pharmaceutical composition), the device terminates (803,805)the qualification process without authorizing provision of the PDE₅inhibitor pharmaceutical agent and, optionally, transmits advice to theuser as to why they should not take the PDE₅ inhibitor pharmaceuticalagent. In some embodiments, this advice is advice to seek immediatemedical attention.

When the sexual intercourse filter is not fired, the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has experienced priapismsince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition and then applies (816) the answer receivedfrom the subject to a priapism filter. When the priapism filter is fired(e.g., when the answer indicates the subject has experienced priapismsince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition), the device terminates (803,805) thequalification process without authorizing provision of the PDE₅inhibitor pharmaceutical agent and, optionally, transmits advice to theuser as to why they should not take the PDE₅ inhibitor pharmaceuticalagent.

When the priapism filter is not fired, the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject has developed vision loss since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical compositionand then applies (818) the answer received from the subject to a sensorydeterioration filter. When the sensory deterioration is fired (e.g.,when the answer indicates the subject has developed sudden vision losssince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition), the device terminates (803,805) thequalification process without authorizing provision of the PDE₅inhibitor pharmaceutical agent and, optionally, transmits advice to theuser as to why they should not take the PDE₅ inhibitor pharmaceuticalagent.

When the sensory deterioration filter is not fired, the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has developed hearing losssince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition and then applies (820) the answer receivedfrom the subject to the sensory deterioration filter. When the sensorydeterioration is fired (e.g., when the answer indicates the subject hasdeveloped sudden hearing loss since receiving their last provision ofthe PDE5 inhibitor pharmaceutical composition), the device terminates(803,805) the qualification process without authorizing provision of thePDE5 inhibitor pharmaceutical agent and, optionally, transmits advice tothe user as to why they should not take the PDE₅ inhibitorpharmaceutical agent. As previously described, in some embodiments theprompts and processes (818,820) associated with the sensorydeterioration filter are combined as a single prompt and process.

When the sensory deterioration filter is not fired, the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has developed a symptom ofheart problems since receiving their last provision of the PDE₅inhibitor pharmaceutical composition and then applies (822) the answerreceived from the subject to a heart problem filter. When the heartproblem filter is fired (e.g. when the answer indicates that the subjecthas developed a heart problem since receiving their las provision of aPDE₅ inhibitor pharmaceutical composition), the device initiates (811-1)an override procedure (e.g., creates a record indicating that the usermust confirm they have discussed taking a PDE₅ inhibitor pharmaceuticalcomposition with a health care provider). When the heart problem filteris not fired (e.g., when the answer indicates the subject has notdeveloped a heart problem), the device proceeds with the qualificationprocess, prompting the subject to provide information indicating apulmonary hypertension status and then applies (824) the answer receivedfrom the subject to a blood pressure filter. When the blood pressurefilter is fired (e.g. when the answer indicates that the subject hasdeveloped pulmonary hypertension since receiving their las provision ofa PDE₅ inhibitor pharmaceutical composition), the device initiates(811-2) an override procedure (e.g., creates a record indicating thatthe user must confirm they have discussed taking a PDE₅ inhibitorpharmaceutical composition with a health care provider). When the bloodpressure filter is not fired, the device proceeds with the qualificationprocess, prompting the subject to provide information indicating a bloodpressure status and then applies (826) the answer received from thesubject to the blood pressure filter. As previously described, in someembodiments the prompts and processes (824,826) associated with theblood pressure filter are combined as a single prompt and process. Whenthe blood pressure filter is fired (e.g. when the answer indicates thatthe subject has developed low blood pressure or uncontrolled high bloodpressure since receiving their las provision of a PDE₅ inhibitorpharmaceutical composition), the device initiates (811-3) an overrideprocedure (e.g., creates a record indicating that the user must confirmthey have discussed taking a PDE₅ inhibitor pharmaceutical compositionwith a health care provider). When the blood pressure filter is notfired (e.g., when the answer indicates the subject has not developed lowblood pressure or uncontrolled high blood pressure), the device proceedswith the qualification process, prompting the subject to provideinformation indicating whether the subject has had a stroke sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition and then applies (828) the answer received from the subjectto a stroke filter. When the stroke filter is fired (e.g. when theanswer indicates that the subject has experienced a stroke sincereceiving their las provision of a PDE₅ inhibitor pharmaceuticalcomposition), the device initiates (811-4) an override procedure (e.g.,creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with ahealth care provider). When the stroke filter is not fired (e.g., whenthe answer indicates the subject has not had a stroke since receivingtheir last provision of the PDE₅ inhibitor), the device proceeds withthe qualification process, prompting the subject to provide informationindicating whether the subject has developed a liver problem sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition and then applies (830) the answer received from the subjectto a liver disease filter. When the liver disease filter is fired (e.g.when the answer indicates that the subject has developed a liver problemsince receiving their last provision of a PDE₅ inhibitor pharmaceuticalcomposition), the device initiates (811-5) an override procedure (e.g.,creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with ahealth care provider). When the liver disease filter is not fired (e.g.,when the answer indicates the subject has not developed a liverproblem), the device proceeds with the qualification process, promptingthe subject to provide information indicating a kidney function statusof the subject and then applies (832) the answer received from thesubject to a kidney disease filter. When the kidney disease filter isfired (e.g. when the answer indicates that the subject has developed akidney disease since receiving their last provision of a PDE₅ inhibitorpharmaceutical composition), the device initiates (811-6) an overrideprocedure (e.g., creates a record indicating that the user must confirmthey have discussed taking a PDE₅ inhibitor pharmaceutical compositionwith a health care provider). When the kidney disease filter is notfired (e.g., when the answer indicates the subject has not developed akidney problem), the device proceeds with the qualification process,prompting the subject to provide information indicating whether thesubject has developed retinitis pigmentosa since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition and thenapplies (834) the answer received from the subject to a retinitispigmentosa filter. When the retinitis pigmentosa filter is fired (e.g.when the answer indicates that the subject has developed retinitispigmentosa since receiving their last provision of a PDE₅ inhibitorpharmaceutical composition) the device initiates (811-7) an overrideprocedure (e.g., creates a record indicating that the user must confirmthey have discussed taking a PDE₅ inhibitor pharmaceutical compositionwith a health care provider). When the retinitis pigmentosa filter isnot fired (e.g., when the answer indicates the subject has not beendiagnosed with retinitis pigmentosa), the device proceeds with thequalification process, prompting the subject to provide informationindicating whether the subject has developed a stomach ulcer sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition and then applies (836) the answer received from the subjectto a stomach ulcer filter. When the stomach ulcer filter is fired (e.g.when the answer indicates that the subject has developed a stomach ulcersince receiving their last provision of a PDE₅ inhibitor pharmaceuticalcomposition), the device initiates (811-8) an override procedure (e.g.,creates a record indicating that the user must confirm they havediscussed taking a PDE₅ inhibitor pharmaceutical composition with ahealth care provider). When the stomach ulcer filter is not fired (e.g.,when the answer indicates the subject has not developed a stomachulcer), the device proceeds with the qualification process, promptingthe subject to provide information indicating whether the subject hasdeveloped a bleeding disorder since receiving their last provision ofthe PDE₅ inhibitor pharmaceutical composition and then applies (838) theanswer received from the subject to a bleeding disorder filter. When thebleeding disorder filter is fired (e.g. when the answer indicates thatthe subject has developed a bleeding disorder since receiving their lastprovision of a PDE₅ inhibitor pharmaceutical composition), the deviceinitiates (811-9) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a health care provider). Whenthe bleeding disorder filter is not fired (e.g., when the answerindicates the subject has not developed a bleeding disorder), the deviceproceeds with the qualification process, prompting the subject toprovide information indicating whether the subject has developed anabnormal genital shape since receiving their last provision of the PDE₅inhibitor pharmaceutical composition and then applies (840) the answerreceived from the subject to a genital abnormality filter. When thegenital abnormality filter is fired (e.g. when the answer indicates thatthe subject has developed pulmonary hypertension since receiving theirlast provision of a PDE₅ inhibitor pharmaceutical composition), thedevice initiates (811-10) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a health care provider). Whenthe genital abnormality filter is not fired (e.g., when the answerindicates the subject has not developed an abnormal penile shape), thedevice proceeds with the qualification process, prompting the subject toprovide information indicating whether the subject has developed a bloodcell disorder since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition and then applies (842) the answer receivedfrom the subject to a blood cell disorder filter. When the blood celldisorder filter is fired (e.g. when the answer indicates that thesubject has developed a blood cell disorder since receiving their lastprovision of a PDE₅ inhibitor pharmaceutical composition), the deviceinitiates (811-11) an override procedure (e.g., creates a recordindicating that the user must confirm they have discussed taking a PDE₅inhibitor pharmaceutical composition with a health care provider).

The device then proceeds with the qualification process, prompting thesubject to provide information indicating whether the subject hasstarted taking a medication that interacts with the PDE₅ inhibitorpharmaceutical composition since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition and then applies (844-854) theanswer received from the subject to a drug interaction filter. Aspreviously described, in some embodiments the drug interaction filtercomprises a plurality of filters, where each filter in the plurality offilters is configured for a specific drug interaction. For instance, insome embodiments the drug interaction filter comprises an alpha blockerfilter, a hypertension medication filter, an HIV protease inhibitorfilter, an oral antifungal, and other medications for treating erectiledysfunction. When the drug interaction filter is fired (e.g., when theanswer indicates the subject is taking a medication that interacts withthe PDE₅ inhibitor pharmaceutical composition), the device initiates(811-12-811-17) an override procedure (e.g., creates a record indicatingthat the user must confirm they have discussed taking a PDE₅ inhibitorpharmaceutical composition with a health care provider).

The device proceeds with the qualification process, determining (855)whether the override procedure has been triggered (e.g., by firing ofone or more of the heart problem filter, the pulmonary hypertensionfilter, the blood pressure filter, the stroke filter, the liver diseasefilter, the kidney problem filter, the retinitis pigmentosa filter, thestomach ulcer filter, the bleeding problem filter, the genitalabnormality filter, the blood cell disorder filter, the alpha blockerfilter, the hypertension medication filter, the HIV protease inhibitorfilter, the oral antifungal filter, the antibiotics filter, and/or theerectile dysfunction medication filter). If the override procedure hasbeen triggered, the device prompts (817) the user to confirm that theyhave spoken with a medical professional about taking a PDE₅ inhibitorpharmaceutical composition (e.g., in view of the underlying risk factorthat triggered the heart problem filter, the pulmonary hypertensionfilter, the blood pressure filter, the stroke filter, the liver diseasefilter, the kidney problem filter, the retinitis pigmentosa filter, thesensory deterioration filter, the stomach ulcer filter, the bleedingproblem filter, the genital abnormality filter, the priapism filter, theblood cell disorder filter, the alpha blocker filter, the hypertensionmedication filter, the HIV protease inhibitor filter, the oralantifungal filter, the antibiotics filter, and/or the erectiledysfunction medication filter) and the medical professional recommendedtaking the PDE₅ inhibitor pharmaceutical composition. If the user'sresponse indicates they have not spoken with a medical professional orthe medical professional did not recommend taking the PDE₅ inhibitorpharmaceutical composition, the device terminates (803, 805) the processand, optionally, transmits advice for the subject to consult a medicalprofessional.

If the override procedure was not triggered, or the override procedurewas triggered and the subject's response indicated that a medicalprofessional recommended they take a PDE₅ inhibitor pharmaceuticalcomposition (e.g., in view of the underlying risk factor triggering theoverride procedure), the device proceeds with the qualification process,prompting (856) the subject to confirm their answers. If the userconfirms their answers, the device transmits (831) a drug facts labelfor the PDE₅ inhibitor pharmaceutical composition and prompts the userto read the drug facts label. If the subject confirms they have read thedrug facts label, the device proceeds to authorize (860) purchase of thePDE₅ inhibitor pharmaceutical composition.

Specific Embodiments

In one aspect, the disclosure provides methods, software, and computersystems for qualifying a human subject for over-the-counter delivery ofa PDE₅ inhibitor pharmaceutical composition for treating erectiledysfunction. In one embodiment, a computer system (e.g., computer system250 in FIG. 2 ) includes instructions for conducting a survey of thesubject (e.g., including survey questions 208 and 212 administered viaassessment module 252 in FIG. 2 ) to obtain information about thesubject necessary to run against at least two series of filters (e.g.,filters 216 and 222 in first filter category class 214-1 and secondfilter category class 220-2, respectively, in FIG. 2 ). The computersystem also includes instructions for running the survey results againstthe filters. Filters 216 in the first series of filters 214 preventauthorization of a provision of the OTC PDE₅ inhibitor where thesubject's survey results identify a contraindication for the OTC PDE₅inhibitor. Filters 222 in the second series of filters 220 generate awarning 226 where the subject's survey results identify a risk factorfor the OTC PDE₅ inhibitor. In some embodiments, the warning 226includes a prompt requiring the subject to confirm they have discussedthe risk factor with a physician in order to proceed with qualificationfor the OTC PDE₅ inhibitor.

In one aspect, the disclosure provides methods, software, and computersystems for re-qualifying a human subject for over-the-counter deliveryof a PDE₅ inhibitor pharmaceutical composition for treating erectiledysfunction. In one embodiment, a computer system (e.g., computer system250 in FIG. 2 ) includes instructions for conducting a survey of thesubject (e.g., administered via reassessment module 254 in FIG. 2 ) toobtain information about the subject necessary to run against at leasttwo series of filters. The computer system also includes instructionsfor running the survey results against the filters. Filters 216 in thethird series of filters prevent authorization for delivery of the OTCPDE₅ inhibitor where the subject's survey results identify acontraindication for the OTC PDE₅ inhibitor. Filters 222 in the fourthseries of filters generate a warning 226 where the subject's surveyresults identify a risk factor for the OTC PDE₅ inhibitor. In someembodiments, the warning 226 includes a prompt requiring the subject toconfirm they have discussed the risk factor with a physician in order toproceed with qualification for the OTC PDE₅ inhibitor.

In one aspect, the disclosure provides a computer system for qualifyinga human subject for over-the-counter delivery of a PDE₅ inhibitorpharmaceutical composition to treat erectile dysfunction. The computersystem comprising one or more processors and a memory, the memorycomprising non-transitory instructions which, when executed by the oneor more processor, perform a method for qualifying a human subject forover-the-counter delivery of the PDE₅ inhibitor pharmaceuticalcomposition. The method includes conducting a first survey of thesubject thereby obtaining a first plurality of survey results necessaryto run against a first plurality of filters of a first category classand a second plurality of filters of a second category class. The methodalso includes running all or a portion of the first plurality of surveyresults against a first plurality of filters of a first category class,wherein, when a respective filter in the first plurality of filters isfired, the subject is deemed not qualified for delivery of the PDE₅inhibitor pharmaceutical composition and the method is terminatedwithout delivery of the PDE₅ inhibitor pharmaceutical composition to thesubject. The method also includes running all or a portion of the firstplurality of survey results against a second plurality of filters of asecond category class, wherein, when a respective filter in the secondplurality of filters is fired, the subject is provided with a warningcorresponding to the respective filter. The method also includesobtaining acknowledgment from the subject for the warning issued to thesubject by any filter in the second plurality of filters. The methodalso includes proceeding with a fulfillment process when no filter inthe first plurality of filters has been fired and the subject hasacknowledged each warning associated with each filter in the secondplurality of filters that was fired. The fulfillment process includes:storing an indication in a subject profile of an initial order for thePDE₅ inhibitor pharmaceutical composition, communicating anover-the-counter drug facts label for the PDE₅ inhibitor pharmaceuticalcomposition to the subject, and authorizing, upon confirmation from thesubject that the over-the-counter drug facts label has been received andread, provision of the PDE₅ inhibitor pharmaceutical composition to thesubject. In some embodiments, the authorization includes a destinationassociated with the subject.

In some embodiments, the first plurality of survey results includes aplurality of survey results selected from the survey results listed inTable 1. In one embodiment, the first plurality of survey resultsindicates: a gender of the subject, an age of the subject, an erectiledysfunction status of the subject, whether the subject is taking anitrate or nitrite vasodilator composition, whether the subject istaking a guanylate cyclase stimulator medication, whether the subject istaking a PDE₅ inhibitor composition, whether the subject has ever had aheart problem, a blood pressure status of the subject, whether thesubject has ever had a stroke, whether the subject has a liver problem,a kidney function status of the subject, whether the subject hasretinitis pigmentosa, whether the subject has developed vision loss,whether the subject has ever had a stomach ulcer, whether the subjecthas a bleeding disorder, a genital status of the subject, whether thesubject has ever experienced priapism, whether the subject has a bloodcell disorder, and whether the subject is taking a medication thatinteracts (e.g., a pharmacokinetic interaction and/or a pharmacodynamicinteraction) with the PDE₅ inhibitor pharmaceutical composition.

In some embodiments, the first plurality of filters includes a pluralityof filters selected from the filters listed in Table 2. In oneembodiment, the first plurality of filters includes a gender filter, anage filter, an erectile dysfunction filter, a vasodilator filter, aguanylate cyclase stimulator filter, and a PDE₅ inhibitor filter.

In some embodiments, the second plurality of filters includes aplurality of filters selected from the filters listed in Table 3. In oneembodiment, the second plurality of filters includes a heart problemfilter, a blood pressure filter, a stroke filter, a liver diseasefilter, a kidney disease filter, a retinitis pigmentosa filter, astomach ulcer filter, a bleeding problem filter, a genital abnormalityfilter, a priapism filter, a blood cell disorder, and a drug interactionfilter.

In some embodiments, the first and second plurality of filters includesfilters selected from the filters listed in Table 8. In someembodiments, the first plurality of filters of the first category classinclude a first sub-plurality of the filters listed in Table 8, forexample, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, orall 19 of the filters listed in Table 8, and the second plurality offilters of the first category class include a second sub-plurality ofthe filters listed in Table 8, which is different from the firstsub-plurality of filters, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, or all 19 of the filters listed in Table 8.In some embodiments, each of the filters in the first sub-plurality offilters is different from each of the filters in the secondsub-plurality of filters (e.g., no filter listed in Table 8 is includedin both the first sub-plurality and the second sub-plurality offilters). In some embodiments, a system for qualifying a subject fordelivery of an over-the-counter PDE₅ inhibitor pharmaceuticalcomposition includes instructions for applying only one plurality offilters, e.g., only filters of a single category class of filters. Insome embodiments, where the method, system, or software applies a singleplurality of filters, the plurality of filters includes a plurality offilters selected from the filters listed in Table 8, e.g., at least 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or all 19 ofthe filters listed in Table 8. In some embodiments, where a filterlisted in Table 8 corresponds to a filter listed in Table 2 or Table 3,a threshold level sufficient to fire the corresponding filter listed inTable 2 or Table 3, as described in detail above, is sufficient to firethe filter listed in Table 8.

TABLE 8 Example filters for qualifying a subject for an over-the-counterprovision of a PDE₅ inhibitor pharmaceutical composition Filter ExampleCriteria  1b a gender filter  2b an age filter  3b an erectiledysfunction filter  4b a vasodilator filter  5b a guanylate cyclasefilter  6b a PDE5 inhibitor filter  7b a heart problem filter  8b ablood pressure filter  9b a stroke filter 10b a liver disease filter 11ba kidney disease filter 12b a retinitis pigmentosa filter 13b a visiondeterioration filter 14b a stomach ulcer filter 15b a bleeding problemfilter 16b a genital abnormality filter 17b a priapism filter 18b ablood cell disorder filter 19b a drug interaction filter

In one aspect, the disclosure provides methods, software, and computersystems for qualifying a human subject for a re-order of anover-the-counter provision of a PDE₅ inhibitor pharmaceuticalcomposition to treat erectile dysfunction. In one embodiment, a computersystem includes instructions, responsive to receiving a re-order requestfrom the subject for the PDE₅ inhibitor pharmaceutical composition, forperforming a re-fulfillment procedure comprising conducting a secondsurvey of the subject thereby obtaining a second plurality of surveyresults necessary to run against a third plurality of filters of a firstcategory class and a fourth plurality of filters of a second categoryclass. The method also includes running all or a portion of the secondplurality of survey results against a third plurality of filters of afirst category class, wherein, when a respective filter in the thirdplurality of filters is fired, the subject is deemed not qualified fordelivery of the PDE₅ inhibitor pharmaceutical composition and the methodis terminated without delivery of the PDE₅ inhibitor pharmaceuticalcomposition to the subject. The method also includes running all or aportion of the second plurality of survey results against a fourthplurality of filters of a second category class, wherein, when arespective filter in the fourth plurality of filters is fired, thesubject is provided with a warning corresponding to the respectivefilter. The method also includes obtaining acknowledgment from thesubject for the warning issued to the subject by any filter in thefourth plurality of filters. The method also includes proceeding with are-fulfillment process when no filter in the third plurality of filtershas been fired and the subject has acknowledged each warning associatedwith each filter in the fourth plurality of filters that was fired. There-fulfillment process includes: storing an indication in a subjectprofile of a re-order for the PDE₅ inhibitor pharmaceutical composition,communicating the over-the-counter drug facts label for PDE₅ inhibitorpharmaceutical composition to the subject, and authorizing, uponconfirmation from the subject that the over-the-counter drug facts labelhas been received and read, provision of the PDE₅ inhibitorpharmaceutical composition to the subject.

In some embodiments, the third series of filters includes one or morefilters listed in Table 5. In some embodiments, the third plurality offilters includes an erectile dysfunction filter, a vasodilator filter, aguanylate cyclase stimulator filter, a PDE₅ inhibitor filter, a sexualintercourse filter, a priapism filter, and a sensory deteriorationfilter.

In some embodiments, the fourth series of filters includes one or morefilters listed in Table 6. In some embodiments, the fourth plurality offilters includes a heart problem filter, a blood pressure filter, astroke filter, a liver disease filter, a kidney disease filter, aretinitis pigmentosa filter, a stomach ulcer filter, a bleeding problemfilter, a genital abnormality filter, a blood cell disorder, and a druginteraction filter.

In some embodiments, the third and fourth plurality of filters includesfilters selected from the filters listed in Table 9. In someembodiments, the third plurality of filters of the first category classinclude a third sub-plurality of the filters listed in Table 9, forexample, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all18 of the filters listed in Table 9, and the fourth plurality of filtersof the first category class include a fourth sub-plurality of thefilters listed in Table 9, which is different from the thirdsub-plurality of filters, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, or all 18 of the filters listed in Table 9. Insome embodiments, each of the filters in the third sub-plurality offilters is different from each of the filters in the fourthsub-plurality of filters (e.g., no filter listed in Table 9 is includedin both the first sub-plurality and the second sub-plurality offilters). In some embodiments, a system for qualifying a subject fordelivery of an over-the-counter PDE₅ inhibitor pharmaceuticalcomposition includes instructions for applying only one plurality offilters, e.g., only filters of a single category class of filters. Insome embodiments, where the method, system, or software applies a singleplurality of filters, the plurality of filters includes a plurality offilters selected from the filters listed in Table 9, e.g., at least 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or all 18 of thefilters listed in Table 9. In some embodiments, where a filter listed inTable 9 corresponds to a filter listed in Table 2, Table 3, Table 5, orTable 6, a threshold level sufficient to fire the corresponding filterlisted in Table 2, Table 3, Table 5, or Table 6, as described in detailabove, is sufficient to fire the filter listed in Table 9.

TABLE 9 Example filters for re-qualifying a subject for anover-the-counter provision of a PDE₅ inhibitor pharmaceuticalcomposition Filter Example Criteria  1b an erectile dysfunction filter 2b a vasodilator filter  3b a guanylate cyclase stimulator filter  4b aPDE₅ inhibitor filter  5b a sexual intercourse filter  6b a priapismfilter  7b a deterioration filter  8b a heart problem filter  9b a bloodpressure filter 10b a stroke filter 11b a liver disease filter 12b akidney disease filter 13b a retinitis pigmentosa filter 14b a stomachulcer filter 15b a bleeding problem filter 16b a genital abnormalityfilter 17b a blood cell disorder filter 18b a drug interaction filter

In one aspect, the present disclosure provides a computer system forqualifying a human subject for over-the-counter delivery of a PDE₅inhibitor pharmaceutical composition for treating erectile dysfunction,the computer system comprising one or more processors and a memory, thememory comprising non-transitory instructions which, when executed bythe one or more processor, perform a method comprising: a) conducting afirst survey of the subject thereby obtaining a first plurality ofsurvey results, wherein the first plurality of survey results indicates:a gender of the subject, an age of the subject, an erectile dysfunctionstatus of the subject, whether the subject is taking a nitrate ornitrite vasodilator composition, whether the subject is taking aguanylate cyclase stimulator medication, whether the subject is taking aPDE₅ inhibitor composition, whether the subject has ever had a heartproblem, a blood pressure status of the subject, whether the subject hasever had a stroke, whether the subject has a liver problem, a kidneyfunction status of the subject, whether the subject has retinitispigmentosa, whether the subject has developed vision loss, whether thesubject has ever had a stomach ulcer, whether the subject has a bleedingdisorder, a genital status of the subject, whether the subject has everexperienced priapism, whether the subject has a blood cell disorder, andwhether the subject is taking a medication that interacts (e.g., apharmacokinetic interaction and/or a pharmacodynamic interaction) withthe PDE₅ inhibitor pharmaceutical composition; b) running all or aportion of the first plurality of survey results against a firstplurality of filters of a first category class, wherein, when arespective filter in the first plurality of filters is fired, thesubject is deemed not qualified for delivery of the PDE₅ inhibitorpharmaceutical composition and the method is terminated without deliveryof the PDE₅ inhibitor pharmaceutical composition to the subject, whereinthe first plurality of filters comprises: a gender filter that is firedwhen the first plurality of survey results indicates that the subject isnot male, an age filter, a first erectile dysfunction filter that isfired at least when the first plurality of survey results indicates thatthe subject does not have erectile dysfunction, a first vasodilatorfilter that is fired at least when the first plurality of survey resultsindicates that the subject is taking a vasodilator compositioncomprising a nitrate or a nitrite, a first guanylate cyclase stimulatorfilter that is fired at least when the first plurality of survey resultsindicates that the subject is taking a guanylate cyclase stimulatormediation, and a first PDE₅ inhibitor filter that is fired at least whenthe first plurality of survey results indicates that the subject istaking a PDE₅ inhibitor composition; c) running all or a portion of thefirst plurality of survey results against a second plurality of filtersof a second category class, wherein, when a respective filter in thesecond plurality of filters is fired, the subject is provided with awarning corresponding to the respective filter, and wherein the secondplurality of filters comprises: a first heart problem filter that isfired at least when the first plurality of survey results indicates thatthe subject has had a heart problem, a first blood pressure filter thatthis fired at least when the first plurality of survey results indicatesthat the subject has either low blood pressure, uncontrolled high bloodpressure, or pulmonary hypertension, a first stroke filter that is firedat least when the first plurality of survey results indicates that thesubject has had a stroke, a first liver disease filter that is fired atleast when the first plurality of survey results indicates that thesubject has a liver problem, a first kidney disease filter that is firedat least when the first plurality of survey results indicates that thesubject has a kidney problem, and a first retinitis pigmentosa filterthat is fired at least when the first plurality of survey resultsindicates that the subject has retinitis pigmentosa, a first visiondeterioration filter that is fired at least when the first plurality ofsurvey results indicates that the subject has had severe vision loss, afirst stomach ulcer filter that is fired at least when the firstplurality of survey results indicates that the subject has had a stomachulcer, a first bleeding problem filter that is fired at least when thefirst plurality of survey results indicates that the subject has ableeding disorder, a first genital abnormality filter that is fired atleast when the first plurality of survey results indicates that thesubject has an abnormal penile shape, a first priapism filter that isfired at least when the first plurality of survey results indicates thatthe subject has experienced priapism, a first blood cell disorder filterthat is fired at least when the first plurality of survey resultsindicates that the subject has a blood cell disorder selected from thegroup consisting of sickle cell anemia, multiple myeloma, and leukemia,a first drug interaction filter that is fired at least when the firstplurality of survey results indicates that the subject is taking amedication that interacts with the PDE₅ inhibitor pharmaceuticalcomposition; d) obtaining acknowledgment from the subject for thewarning issued to the subject by any filter in the second plurality offilters; and e) proceeding with a fulfillment process when (i) no filterin the first plurality of filters has been fired and (ii) the subjecthas acknowledged each warning associated with each filter in the secondplurality of filters that was fired, wherein the fulfillment processcomprises: storing an indication in a subject profile of an initialorder for the PDE₅ inhibitor pharmaceutical composition, communicatingan over-the-counter drug facts label for the PDE₅ inhibitorpharmaceutical composition to the subject, and authorizing, uponconfirmation from the subject that the over-the-counter drug facts labelhas been received and read, provision of the PDE₅ inhibitorpharmaceutical composition to the subject.

In some embodiments, the PDE₅ inhibitor pharmaceutical composition hasthe structure:

where: R⁰ represents hydrogen, halogen or C₁₋₆ alkyl; R¹ representshydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, haloC₁₋₆ alkyl, C₃₋₈cycloalkyl, C₃₋₈ cycloalkyl-C₁₋₃ alkyl, arylC₁₋₃ alkyl or heteroarylC₁₋₃alkyl; R² represents an optionally substituted mono-cyclic aromatic ringselected from benzene, thiophene, furan and pyridine or an optionallysubstituted bicyclic ring

attached to the rest of the molecule via one of the benzene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which maybe saturated or partially or fully unsaturated and comprises carbonatoms and optionally one or two heteroatoms selected from oxygen,sulphur and nitrogen; and R³ represents hydrogen or C1-3 alkyl, or R¹and R³ together represent a 3- or 4-membered alkyl or alkenyl chain, ora pharmaceutically acceptable salt thereof.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes tadalafil. In some embodiments, the PDE₅ inhibitor includes apharmaceutically acceptable salt of tadalafil.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of from 2.5 mg to 10 mg oftadalafil no more than once per day.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of 5 mg of tadalafil no more thanonce per day.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes vardenafil.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of from 2.5 mg to 20 mg ofvardenafil no more than once per day.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of 5 mg of vardenafil no more thanonce per day.

In some embodiments, the age filter is fired when the first plurality ofsurvey results indicates that the subject is less than eighteen yearsold.

In some embodiments, the vasodilator composition, which is capable offiring the first vasodilator filter, includes a compound selected fromthe group consisting of nitroglycerin, amyl nitrate, amyl nitrite, andbutyl nitrate.

In some embodiments, the heart problem, which is capable of firing thefirst heart problem filter, is selected from the group consisting of aheart attack, arrhythmia, angina, chest pain, narrowing of the aorticvalve, and heart failure.

In some embodiments, the first drug interaction filter is fired when thefirst plurality of survey results indicates that the subject is taking amedication selected from the group consisting of an alpha blocker, anHIV protease inhibitor, an antifungal medication, an antibiotic, a bloodpressure medication, and an erectile dysfunction medication.

In some embodiments, the warning corresponding to a respective filter inthe second plurality of filters comprises a prompt for the subject toindicate whether they have discussed the risk factor underlying therespective filter in the second plurality of filters that was fired witha health care provider. Acknowledgement is obtained from the subjectwhen the subject indicates that they have discussed the risk factorunderlying the respective filter in the second plurality of filters thatwas fired with a health care provider.

In some embodiments, the fulfillment process further comprises storing adestination associated with the subject in the subject profile.

In some embodiments, coordinating shipping of the PDE₅ inhibitorpharmaceutical composition to a physical address associated with thesubject.

In some embodiments of the aspects disclosed above, the method furthercomprises: f) responsive to receiving a re-order request from thesubject for the PDE₅ inhibitor pharmaceutical composition, performing are-fulfillment procedure comprising: (i) conducting a second survey ofthe subject thereby obtaining a second plurality of survey results,wherein the second plurality of survey results indicates: an erectiledysfunction status of the subject, whether the subject has started totake a nitrate or nitrite vasodilator composition since receiving theirlast provision of the PDE₅ inhibitor pharmaceutical composition, whetherthe subject has started to take a guanylate cyclase stimulatormedication since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, whether the subject has started to take aPDE₅ inhibitor composition since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, whether the subject hasdeveloped symptoms of heart problems during sexual intercourse sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, whether the subject has experienced priapism sincereceiving their last provision of the PDE5 inhibitor pharmaceuticalcomposition, whether the subject has developed hearing or vision losssince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, whether the subject has developed symptomsof heart problems since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, a blood pressure status of thesubject, whether the subject has had a stroke since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition, whether thesubject has developed a liver problem since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition, a kidneyfunction status of the subject, whether the subject has developedretinitis pigmentosa since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developeda stomach ulcer since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developeda bleeding disorder since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, whether the subject has developedan abnormal genital shape since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, whether the subject hasdeveloped a blood cell disorder since receiving their last provision ofthe PDE₅ inhibitor pharmaceutical composition, and whether the subjecthas started taking a medication that interacts with the PDE₅ inhibitorpharmaceutical composition since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition; (ii) running all or a portionof the second plurality of survey results against a third plurality offilters of the first category class, wherein, when a respective filterin the third plurality of filters is fired, the subject is deemed notqualified for the PDE₅ inhibitor pharmaceutical composition and there-fulfillment process is terminated without delivery of the PDE₅inhibitor pharmaceutical composition to the subject, wherein the thirdplurality of filters comprise: a second erectile dysfunction filter thatis fired at least when the second plurality of survey results indicatesthat the subject does not have erectile dysfunction, a secondvasodilator filter that is fired at least when the second plurality ofsurvey results indicates that the subject is taking a vasodilatorcomposition comprising a nitrate or a nitrite, a second guanylatecyclase stimulator filter that is fired at least when the secondplurality of survey results indicates that the subject is taking aguanylate cyclase stimulator mediation, a second PDE₅ inhibitor filterthat is fired at least when the second plurality of survey resultsindicates that the subject is taking a PDE₅ inhibitor composition, asexual intercourse filter that is fired at least when the secondplurality of survey results indicates that the subject has developedsymptoms of heart problems during sexual intercourse since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition, asecond priapism filter that is fired at least when the second pluralityof survey results indicates that the subject has had priapism sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, and a sensory deterioration filter that is fired at leastwhen the second plurality of survey results indicates that the subjecthas developed sudden vision loss or sudden hearing loss since receivingtheir last provision of the cGMP-specific phosphodiesterase 5 (PDE₅)inhibitor pharmaceutical composition; (iii) running all or a portion ofthe second plurality of survey results against a fourth plurality offilters of the second category class, wherein, when a respective filterin the fourth plurality of filters is fired, the subject is providedwith a warning corresponding to the respective filter, and wherein thefourth plurality of filters comprises: a second heart problem filterthat is fired at least when the second plurality of survey resultsindicates that the subject has developed a heart problem since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition, asecond blood pressure filter that this fired at least when the secondplurality of survey results indicates that the subject has developedeither low blood pressure, uncontrolled high blood pressure, orpulmonary hypertension, a second stroke filter that is fired at leastwhen the second plurality of survey results indicates that the subjecthas had a stroke since receiving their last provision of the PDE₅inhibitor pharmaceutical composition, a second liver disease filter thatis fired at least when the second plurality of survey results indicatesthat the subject has developed liver disease since receiving their lastprovision of the PDE₅ inhibitor pharmaceutical composition, a secondkidney disease filter that is fired at least when the second pluralityof survey results indicates that the subject has developed a kidneyproblem since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, a second retinitis pigmentosa filter that isfired at least when the second plurality of survey results indicatesthat the subject has been diagnosed with retinitis pigmentosa sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, a second stomach ulcer filter that is fired at least whenthe second plurality of survey results indicates that the subject hasdeveloped a stomach ulcer since receiving their last provision of thePDE₅ inhibitor pharmaceutical composition, a second bleeding problemfilter that is fired at least when the second plurality of surveyresults indicates that the subject has developed a bleeding disordersince receiving their last provision of the PDE₅ inhibitorpharmaceutical composition, a second genital abnormality filter that isfired at least when the second plurality of survey results indicatesthat the subject has developed an abnormal genital shape since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition, asecond blood cell disorder filter that is fired at least when the secondplurality of survey results indicates that the subject has developed ablood disorder selected from the group consisting of sickle cell anemia,multiple myeloma, and leukemia, since receiving their last provision ofthe PDE₅ inhibitor pharmaceutical composition, and a second druginteraction filter that is fired at least when the second plurality ofsurvey results indicates that the subject has started taking amedication that interacts with the PDE₅ inhibitor pharmaceuticalcomposition since receiving their last provision of the PDE₅ inhibitorpharmaceutical composition; (iv) obtaining acknowledgment from thesubject for the warning issued to the subject by any filter in thefourth plurality of filters; and (v) proceeding with the re-fulfillmentprocess when (a) the re-fulfillment process is not already terminated bythe firing of a filter in the third plurality of filters and (b) thesubject has acknowledged each warning associated with each filter in thefourth plurality of filters that was fired, wherein the re-fulfillmentprocess further comprises: storing an indication in the subject profileof a re-order for the PDE₅ inhibitor pharmaceutical composition,communicating the over-the-counter drug facts label for the PDE₅inhibitor pharmaceutical composition to the subject, and authorizing,upon confirmation from the subject that the over-the-counter drug factslabel has been received and read, a re-order provision of the PDE₅inhibitor pharmaceutical composition to the subject.

In some embodiments of the aspects disclosed above, the second pluralityof survey results further comprises whether the subject has side effectsassociated with the PDE₅ inhibitor pharmaceutical composition sincereceiving their last provision of the PDE₅ inhibitor pharmaceuticalcomposition, and the fourth plurality of filters further comprises aside effect filter that is fired at least when the second plurality ofsurvey results indicates that the subject has developed, since receivingtheir last provision of the PDE₅ inhibitor pharmaceutical composition, aside effect selected from the group consisting of headaches, abnormalvision, muscle pain, nausea, dizziness, and a skin rash.

In some embodiments of the aspects disclosed above, the re-fulfillmentprocess further comprises, when a respective filter in the thirdplurality of filters or fourth plurality of filters is fired, storing arecord associated with the firing of the respective filter in an adverseevent profile comprising records of filter firing events associated witha plurality of subjects.

In one aspect, the disclosure provides a method for treating erectiledysfunction in a subject in need thereof, the method comprising:administering a (e.g., low-dose) PDE₅ inhibitor pharmaceuticalcomposition to a subject qualified for over-the-counter access to thePDE₅ inhibitor pharmaceutical composition. In some embodiments, thesubject is qualified for the over-the-counter access to the PDE₅inhibitor composition using a method, system, or computer readablemedium disclosed herein.

In some embodiments, the PDE₅ inhibitor pharmaceutical composition hasthe structure:

where: R⁰ represents hydrogen, halogen or C₁₋₆ alkyl; R¹ representshydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, haloC₁₋₆ alkyl, C₃₋₈cycloalkyl, C₃₋₈ cycloalkyl-C₁₋₃ alkyl, arylC₁₋₃ alkyl or heteroarylC₁₋₃alkyl; R² represents an optionally substituted mono-cyclic aromatic ringselected from benzene, thiophene, furan and pyridine or an optionallysubstituted bicyclic ring

attached to the rest of the molecule via one of the benzene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which maybe saturated or partially or fully unsaturated and comprises carbonatoms and optionally one or two heteroatoms selected from oxygen,sulphur and nitrogen; and R³ represents hydrogen or C1-3 alkyl, or R¹and R³ together represent a 3- or 4-membered alkyl or alkenyl chain, ora pharmaceutically acceptable salt thereof.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes tadalafil or a pharmaceutically acceptable salt thereof.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of from 2.5 mg to 10 mg oftadalafil no more than once per day.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of 5 mg of tadalafil no more thanonce per day.

In some embodiments, the PDE₅ inhibitor pharmaceutical compositionincludes vardenafil.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of from 2.5 mg to 20 mg ofvardenafil no more than once per day.

In some embodiments, upon confirmation from the subject that the overthe counter drug facts label has been received and read, the subject isauthorized for provision of a dosage of 5 mg of vardenafil no more thanonce per day.

In some embodiments, the disclosure provides methods for treatingerectile dysfunction with an over the counter cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition. Themethod includes providing a first survey for obtaining a firstinformation set from the human, via a computer system having a processorprogramed to perform the first survey, where the first information setincludes information about the human that relates to potential riskfactors and contraindications for the cGMP-specific phosphodiesterase 5(PDE₅) inhibitor pharmaceutical composition, as described herein. Themethod also includes applying an algorithm to the first information set,via a computer system having a processor programed to perform thealgorithm. The algorithm runs all or a portion of the first informationset against a first plurality of filters, where the human is deemed notqualified for treatment with the over the counter cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition fortreating erectile dysfunction when a respective filter in the firstplurality of filters is fired and the method is terminated withoutauthorizing provision of the cGMP-specific phosphodiesterase 5 (PDE₅)inhibitor pharmaceutical composition to the human, where the firstplurality of filters includes filters related to contraindications ofthe cGMP-specific phosphodiesterase 5 (PDE₅) inhibitor pharmaceuticalcomposition as described herein. The algorithm also runs all or aportion of the first information set against a second plurality offilters, where, when a respective filter in the second plurality offilters is fired, the human is provided with a warning corresponding tothe respective filter, and where the second plurality of filtersincludes filters related to risk factors for the cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition asdescribed herein. The algorithm also obtains acknowledgment from thehuman of the risk factor associated with each warning issued to thehuman by any filter in the second plurality of filters. In someembodiments, the acknowledgement includes confirmation that the humanhas discussed the risk factor with a physician. The algorithm proceedswith a fulfillment process when (a) no filter in the first plurality offilters has been fired and (b) the human has acknowledged each warningassociated with each filter in the second plurality of filters that wasfired. The fulfillment process includes storing an indication in asubject profile of an initial order for the cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition,communicating an over the counter drug facts label for the cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition to thehuman, and authorizing, upon confirmation from the subject that the overthe counter drug facts label has been received and read, provision ofthe cGMP-specific phosphodiesterase 5 (PDE₅) inhibitor pharmaceuticalcomposition to the human, where the authorization includes a destinationassociated with the subject. In some embodiments, the method alsoincludes treating the human to treat erectile dysfunction of the human,upon authorization of the provision e.g., by providing access to thecGMP-specific phosphodiesterase 5 (PDE₅) inhibitor pharmaceuticalcomposition to the human and/or by administering the cGMP-specificphosphodiesterase 5 (PDE₅) inhibitor pharmaceutical composition to treaterectile dysfunction in the human.

EXAMPLES

Example 1: A computer system is configured for qualifying a subject forover-the-counter delivery of an tadalafil pharmaceutical composition(e.g.,(6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione)to treat erectile dysfunction. The computer system includes instructionsfor conducting a survey of the subject. The survey is utilized to obtainone or more results of: a gender of the subject, an age of the subject,an erectile dysfunction status of the subject, whether the subject istaking a nitrate or nitrite vasodilator composition, whether the subjectis taking a guanylate cyclase stimulator medication, whether the subjectis taking a PDE₅ inhibitor composition, whether the subject has ever hada heart problem, a blood pressure status of the subject, whether thesubject has ever had a stroke, whether the subject has a liver problem,a kidney function status of the subject, whether the subject hasretinitis pigmentosa, whether the subject has developed vision loss,whether the subject has ever had a stomach ulcer, whether the subjecthas a bleeding disorder, a genital status of the subject, whether thesubject has ever experienced priapism, whether the subject has a bloodcell disorder, and whether the subject is taking a medication thatinteracts (e.g., a pharmacokinetic interaction and/or a pharmacodynamicinteraction) with the tadalafil pharmaceutical composition.

The computer system runs survey results against a first series offilters that are each associated with a first filter category class. Thefirst filter category class is configured to prevent authorization forOTC delivery of the OTC tadalafil when the subject's survey resultsidentify a contraindication for the tadalafil. In some embodiments, thefirst series of filters includes one or more of a gender filter, an agefilter, a first erectile dysfunction filter, a first vasodilator filter,a first guanylate cyclase stimulator filter, and a first PDE₅ inhibitorfilter. The gender filter is configured to ensure the subject is male.The age filter is configured to ensure that the subject is eighteenyears old or older. The erectile dysfunction filter is configured toensure the subject has erectile dysfunction. The vasodilator filter isconfigured to ensure the subject is not taking an organic nitrate ornitrite. The guanylate cyclase stimulator is configured to ensure thesubject is not taking a guanylate cyclase stimulator. Furthermore, thePDE₅ inhibitor is configured to ensure the subject is not takingadditional PDE₅ inhibitors.

The computer system runs survey results against a second series offilters that each generates a warning where the subject's survey resultsidentify a risk factor for the OTC tadalafil. In some embodiments, thesecond series of filters comprises a first heart problem filter, a firstblood pressure filter, a first stroke filter, a first liver diseasefilter, a first kidney disease filter, a first retinitis pigmentosafilter, a first stomach ulcer filter, a first bleeding problem filter, afirst genital abnormality filter, a first priapism filter, a first bloodcell disorder, and a first drug interaction filter. The first heartproblem filter is configured to ensure the subject has not developedheart problems. The first stroke filter is configured to ensure thesubject has not had a stroke. The first liver disease filter isconfigured to ensure that the subject has adequate liver function. Thefirst kidney disease filter is configured to ensure that the subject hasadequate kidney function. The first retinitis pigmentosa filter isconfigured to ensure that the subject does not have a variety of visionconditions. The first stomach ulcer filter is configured to ensure thatthe subject has not had a stomach ulcer. The first bleeding problemfilter is configured to ensure that the subject does not have a bleedingproblem (e.g., a coagulation problem). The first genital abnormalityfilter is configured to ensure that the subject has a normal penileshape. The first priapism filter is configured to ensure that thesubject has not experienced priapism. The first blood cell disorderfilter is configured to ensure the subject has normal blood cells. Thefirst drug interaction filter is configured to ensure the subject is nottaking a substance that interacts with tadalafil. Substances thatinteract with tadalafil, and are therefore capable of firing the firstdrug interaction filter, include an alpha blocker (e.g., terazosin,tamsulosin, doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride andtamsulosin HCl, and silodosin), an HIV protease inhibitor (e.g.,ritonavir), an antifungal medication (e.g., ketoconazole anditraconazole), an antibiotic (e.g., clarithromycin, telithromycin, anderythromycin), a blood pressure medication (e.g., a medication to treathypertension), and an erectile dysfunction medication.

The computer system then prompts the subject to acknowledge or denyhaving discussed these warnings with a medical professional (e.g., theirphysician or healthcare provider). The computer system then proceedswith a fulfillment process only when none of the first series of filterswas fired and the subject acknowledged that they discussed each warningissued in association with the second series of filters that was fired.

The computer system stores an indication of an initial order of the OTCtadalafil in a subject profile, and communicates an over-the-counterdrug facts label for the tadalafil pharmaceutical composition to thesubject. Upon confirmation from the subject that they have received andread the over-the-counter drug facts label, the computer systemauthorizes provision of the OTC tadalafil pharmaceutical composition tothe subject.

In some embodiments, the computer system includes instructions forconducting another survey of the subject responsive to a re-orderrequest of the tadalafil pharmaceutical composition. This survey isutilized to obtain one or more results of: an erectile dysfunctionstatus of the subject, whether the subject has started to take a nitrateor nitrite vasodilator composition since receiving their last provisionof tadalafil, whether the subject has started to take a guanylatecyclase stimulator medication since receiving their last provision oftadalafil, whether the subject has started to take a PDE₅ inhibitorcomposition since receiving their last provision of tadalafil, whetherthe subject has developed symptoms of heart problems during sexualintercourse since receiving their last provision of tadalafil, whetherthe subject has experienced priapism since receiving their lastprovision of tadalafil, whether the subject has developed hearing orvision loss since receiving their last provision of tadalafil, whetherthe subject has developed a symptom of heart problems since receivingtheir last provision of tadalafil, a blood pressure status of thesubject, whether the subject has had a stroke since receiving their lastprovision of tadalafil, whether the subject has developed a liverproblem since receiving their last provision of tadalafil, a kidneyfunction status of the subject, whether the subject has developedretinitis pigmentosa since receiving their last provision of tadalafil,whether the subject has developed a stomach ulcer since receiving theirlast provision of tadalafil, whether the subject has developed ableeding disorder since receiving their last provision of tadalafil,whether the subject has developed an abnormal genital shape sincereceiving their last provision of tadalafil, whether the subject hasdeveloped a blood cell disorder since receiving their last provision oftadalafil, and whether the subject has started taking a medication thatinteracts with tadalafil since receiving their last provision oftadalafil.

The computer system runs survey results against a third series offilters that are each associated with the first filter category class.In some embodiments, the third series of filters includes one or more ofa second erectile dysfunction filter, a second vasodilator filter, asecond guanylate cyclase stimulator filter, a second PDE₅ inhibitorfilter, a sexual intercourse filter, a second priapism filter, and asensory deterioration filter. The second erectile dysfunction filter isconfigured to ensure the subject has erectile dysfunction. The secondvasodilator filter is configured to ensure the subject is not taking anorganic nitrate or nitrite since receiving their last provision oftadalafil. The second guanylate cyclase stimulator is configured toensure the subject is not taking a guanylate cyclase stimulator sincereceiving their last provision of tadalafil. The second PDE₅ inhibitoris configured to ensure the subject is not taking additional PDE₅inhibitors since receiving their last provision of tadalafil. The sexualintercourse filter is configured to ensure the subject has not developedheart problems during sexual intercourse since receiving their lastprovision of tadalafil. The second priapism filter is configured toensure that the subject has not experienced priapism since receivingtheir last provision of tadalafil. The sensory deterioration filter isconfigured to ensure that the subject has not developed hearing loss orvision loss since receiving their last provision of tadalafil.

The computer system runs survey results against a fourth series offilters that each generates a warning where the subject's survey resultsidentify a risk factor for the OTC tadalafil. In some embodiments, thefourth series of filters comprises a second heart problem filter, asecond blood pressure filter, a second stroke filter, a second liverdisease filter, a second kidney disease filter, a second retinitispigmentosa filter, a second stomach ulcer filter, a second bleedingproblem filter, a second genital abnormality filter, a second blood celldisorder, and a second drug interaction filter. The second heart problemfilter is configured to ensure the subject has not developed heartproblems since receiving their last provision of tadalafil. The secondstroke filter is configured to ensure the subject has not had a strokesince receiving their last provision of tadalafil. The second liverdisease filter is configured to ensure that the subject has adequateliver function since receiving their last provision of tadalafil. Thesecond kidney disease filter is configured to ensure that the subjecthas adequate kidney function since receiving their last provision oftadalafil. The second retinitis pigmentosa filter is configured toensure that the subject has not developed a variety of vision conditionssince receiving their last provision of tadalafil. The second stomachulcer filter is configured to ensure that the subject has not had astomach ulcer since receiving their last provision of tadalafil. Thesecond bleeding problem filter is configured to ensure that the subjectdoes not have a bleeding problem (e.g., a coagulation problem) sincereceiving their last provision of tadalafil. The second genitalabnormality filter is configured to ensure that the subject has a normalpenile shape since receiving their last provision of tadalafil. Thesecond priapism filter is configured to ensure that the subject has notexperienced priapism since receiving their last provision of tadalafil.The second blood cell disorder filter is configured to ensure thesubject has normal blood cells since receiving their last provision oftadalafil. The second drug interaction filter is configured to ensurethe subject is not taking a substance that interacts with tadalafilsince receiving their last provision of tadalafil. Substances thatinteract with tadalafil, and are therefore capable of firing the firstdrug interaction filter, include an alpha blocker (e.g., terazosin,tamsulosin, doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride andtamsulosin HCl, and silodosin), an HIV protease inhibitor (e.g.,ritonavir), an antifungal medication (e.g., ketoconazole anditraconazole), an antibiotic (e.g., clarithromycin, telithromycin, anderythromycin), a blood pressure medication (e.g., a medication to treathypertension), and an erectile dysfunction medication.

The computer system then prompts the subject to acknowledge or denyhaving discussed these warnings with a medical professional (e.g., theirphysician or healthcare provider). The computer system then proceedswith a re-fulfillment process only when none of the third series offilters was fired the subject acknowledged that they discussed eachwarning issued in association with the fourth series of filters that wasfired.

The computer system stores an indication of a re-order of the OTCtadalafil in the subject profile, and communicates the over-the-counterdrug facts label for the tadalafil pharmaceutical composition to thesubject. Upon confirmation from the subject that they have received andread the over-the-counter drug facts label, the computer systemauthorizes provision of the OTC tadalafil pharmaceutical composition tothe subject.

Example 2: A computer system is configured for qualifying a subject forover-the-counter delivery of a vardenafil pharmaceutical composition(e.g.,4-[2-Ethoxy-5-(4-ethylpiperazin-1-yl)sulfonyl-phenyl]-9-methyl-7-propyl-3,5,6,8-tetrazabicyclo[4.3.0]nona-3,7,9-trien-2-one)to treat erectile dysfunction. The computer system includes instructionsfor conducting a survey of the subject. The survey is utilized to obtainone or more results of: a gender of the subject, an age of the subject,an erectile dysfunction status of the subject, whether the subject istaking a nitrate or nitrite vasodilator composition, whether the subjectis taking a guanylate cyclase stimulator medication, whether the subjectis taking a PDE₅ inhibitor composition, whether the subject has ever hada heart problem, a blood pressure status of the subject, whether thesubject has ever had a stroke, whether the subject has a liver problem,a kidney function status of the subject, whether the subject hasretinitis pigmentosa, whether the subject has developed vision loss,whether the subject has ever had a stomach ulcer, whether the subjecthas a bleeding disorder, a genital status of the subject, whether thesubject has ever experienced priapism, whether the subject has a bloodcell disorder, and whether the subject is taking a medication thatinteracts (e.g., a pharmacokinetic interaction and/or a pharmacodynamicinteraction) with the vardenafil pharmaceutical composition.

The computer system runs survey results against a first series offilters that are each associated with a first filter category class. Thefirst filter category class is configured to prevent authorization forOTC delivery of the OTC vardenafil when the subject's survey resultsidentify a contraindication for the vardenafil. In some embodiments, thefirst series of filters includes one or more of a gender filter, an agefilter, a first erectile dysfunction filter, a first vasodilator filter,a first PDE₅ inhibitor filter, and a first guanylate cyclase stimulatorfilter. The gender filter is configured to ensure the subject is male.The age filter is configured to ensure that the subject is over eighteenyears old. The erectile dysfunction filter is configured to ensure thesubject has erectile dysfunction. The vasodilator filter is configuredto ensure the subject is not taking an organic nitrate or nitrite. ThePDE₅ inhibitor is configured to ensure the subject is not takingadditional PDE₅ inhibitors. Furthermore, the guanylate cyclasestimulator is configured to ensure the subject is not taking a guanylatecyclase stimulator.

The computer system runs survey results against a second series offilters that each generates a warning where the subject's survey resultsidentify a risk factor for the OTC vardenafil. In some embodiments, thesecond series of filters comprises a first heart problem filter, a firstblood pressure filter, a first stroke filter, a first liver diseasefilter, a first kidney disease filter, a first retinitis pigmentosafilter, a first stomach ulcer filter, a first bleeding problem filter, afirst genital abnormality filter, a first priapism filter, a first bloodcell disorder, and a first drug interaction filter. The first heartproblem filter is configured to ensure the subject has not developed aheart problem. The first stroke filter is configured to ensure thesubject has not had a stroke. The first liver disease filter isconfigured to ensure that the subject has adequate liver function. Thefirst kidney disease filter is configured to ensure that the subject hasadequate kidney function. The first retinitis pigmentosa filter isconfigured to ensure that the subject does not have a variety of visionconditions. The first stomach ulcer filter is configured to ensure thatthe subject has not had a stomach ulcer. The first bleeding problemfilter is configured to ensure that the subject does not have a bleedingproblem (e.g., a coagulation problem). The first genital abnormalityfilter is configured to ensure that the subject has a normal penileshape. The first priapism filter is configured to ensure that thesubject has not experienced priapism. The first blood cell disorderfilter is configured to ensure the subject has normal blood cells. Thefirst drug interaction filter is configured to ensure the subject is nottaking a substance that interacts with vardenafil. Substances thatinteract with vardenafil, and are therefore capable of firing the firstdrug interaction filter, include an alpha blocker (e.g., terazosin,tamsulosin, doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride andtamsulosin HCl, and silodosin), an HIV protease inhibitor (e.g.,ritonavir), an antifungal medication (e.g., ketoconazole anditraconazole), an antibiotic (e.g., clarithromycin, telithromycin, anderythromycin), a blood pressure medication (e.g., a medication to treathypertension), and an erectile dysfunction medication.

The computer system then prompts the subject to acknowledge or denyhaving discussed these warnings with a medical professional (e.g., theirphysician or healthcare provider). The computer system then proceedswith a fulfillment process only when none of the first series of filterswas fired and the subject acknowledged that they discussed each warningissued in association with the second series of filters that was fired.

The computer system stores an indication of an initial order of the OTCvardenafil in a subject profile, and communicates an over-the-counterdrug facts label for the vardenafil pharmaceutical composition to thesubject. Upon confirmation from the subject that they have received andread the over-the-counter drug facts label, the computer systemauthorizes provision of the OTC vardenafil pharmaceutical composition tothe subject.

In some embodiments, the computer system includes instructions forconducting another survey of the subject responsive to a re-orderrequest of the vardenafil pharmaceutical composition. This survey isutilized to obtain one or more results of: an erectile dysfunctionstatus of the subject, whether the subject has started to take a nitrateor nitrite vasodilator composition since receiving their last provisionof vardenafil, whether the subject has started to take a guanylatecyclase stimulator medication since receiving their last provision ofvardenafil, whether the subject has started to take a PDE₅ inhibitorcomposition since receiving their last provision of vardenafil, whetherthe subject has developed symptoms of heart problems during sexualintercourse since receiving their last provision of vardenafil, whetherthe subject has experienced priapism since receiving their lastprovision of vardenafil, whether the subject has developed hearing orvision loss since receiving their last provision of vardenafil, whetherthe subject has developed a symptom of heart problems since receivingtheir last provision of vardenafil, a blood pressure status of thesubject, whether the subject has had a stroke since receiving their lastprovision of vardenafil, whether the subject has developed a liverproblem since receiving their last provision of vardenafil, a kidneyfunction status of the subject, whether the subject has developedretinitis pigmentosa since receiving their last provision of vardenafil,whether the subject has developed a stomach ulcer since receiving theirlast provision of vardenafil, whether the subject has developed ableeding disorder since receiving their last provision of vardenafil,whether the subject has developed an abnormal genital shape sincereceiving their last provision of vardenafil, whether the subject hasdeveloped a blood cell disorder since receiving their last provision ofvardenafil, and whether the subject has started taking a medication thatinteracts with vardenafil since receiving their last provision ofvardenafil.

The computer system runs survey results against a third series offilters that are each associated with the first filter category class.In some embodiments, the third series of filters includes one or more ofa second erectile dysfunction filter, a second vasodilator filter, asecond guanylate cyclase stimulator filter, a second PDE₅ inhibitorfilter, a sexual intercourse filter, a second priapism filter, and asensory deterioration filter. The second erectile dysfunction filter isconfigured to ensure the subject has erectile dysfunction. The secondvasodilator filter is configured to ensure the subject is not taking anorganic nitrate or nitrite since receiving their last provision ofvardenafil. The second guanylate cyclase stimulator is configured toensure the subject is not taking a guanylate cyclase stimulator sincereceiving their last provision of vardenafil. The second PDE₅ inhibitoris configured to ensure the subject is not taking additional PDE₅inhibitors since receiving their last provision of vardenafil. Thesexual intercourse filter is configured to ensure the subject has notdeveloped heart problems during sexual intercourse since receiving theirlast provision of vardenafil. The second priapism filter is configuredto ensure that the subject has not experienced priapism since receivingtheir last provision of vardenafil. The sensory deterioration filter isconfigured to ensure that the subject has not developed hearing loss orvision loss since receiving their last provision of vardenafil.

The computer system runs survey results against a fourth series offilters that each generates a warning where the subject's survey resultsidentify a risk factor for the OTC vardenafil. In some embodiments, thefourth series of filters comprises a second heart problem filter, asecond blood pressure filter, a second stroke filter, a second liverdisease filter, a second kidney disease filter, a second retinitispigmentosa filter, a second stomach ulcer filter, a second bleedingproblem filter, a second genital abnormality filter, a second blood celldisorder, and a second drug interaction filter. The second heart problemfilter is configured to ensure the subject has not developed a heartproblem since receiving their last provision of vardenafil. The secondstroke filter is configured to ensure the subject has not had a strokesince receiving their last provision of vardenafil. The second liverdisease filter is configured to ensure that the subject has adequateliver function since receiving their last provision of vardenafil. Thesecond kidney disease filter is configured to ensure that the subjecthas adequate kidney function since receiving their last provision ofvardenafil. The second retinitis pigmentosa filter is configured toensure that the subject does not have a variety of vision conditionssince receiving their last provision of vardenafil. The second stomachulcer filter is configured to ensure that the subject has not had astomach ulcer since receiving their last provision of vardenafil. Thesecond bleeding problem filter is configured to ensure that the subjectdoes not have a bleeding problem (e.g., a coagulation problem) sincereceiving their last provision of vardenafil. The second genitalabnormality filter is configured to ensure that the subject has a normalpenile shape since receiving their last provision of vardenafil. Thesecond priapism filter is configured to ensure that the subject has notexperienced priapism since receiving their last provision of vardenafil.The second blood cell disorder filter is configured to ensure thesubject has normal blood cells since receiving their last provision ofvardenafil. The second drug interaction filter is configured to ensurethe subject is not taking a substance that interacts with vardenafilsince receiving their last provision of vardenafil. Substances thatinteract with vardenafil, and are therefore capable of firing the firstdrug interaction filter, include an alpha blocker (e.g., terazosin,tamsulosin, doxazosin mesylate, prazosin HCl, alfuzosin, dutasteride andtamsulosin HCl, and silodosin), an HIV protease inhibitor (e.g.,ritonavir), an antifungal medication (e.g., ketoconazole anditraconazole), an antibiotic (e.g., clarithromycin, telithromycin, anderythromycin), a blood pressure medication (e.g., a medication to treathypertension), and an erectile dysfunction medication.

The computer system then prompts the subject to acknowledge or denyhaving discussed these warnings with a medical professional (e.g., theirphysician or healthcare provider). The computer system then proceedswith a re-fulfillment process only when none of the third series offilters was fired the subject acknowledged that they discussed eachwarning issued in association with the fourth series of filters that wasfired.

The computer system stores an indication of a re-order of the OTCvardenafil in the subject profile, and communicates the over-the-counterdrug facts label for the vardenafil pharmaceutical composition to thesubject. Upon confirmation from the subject that they have received andread the over-the-counter drug facts label, the computer systemauthorizes provision of the OTC vardenafil pharmaceutical composition tothe subject.

REFERENCES CITED AND ALTERNATIVE EMBODIMENTS

All references cited herein are incorporated herein by reference intheir entirety and for all purposes to the same extent as if eachindividual publication or patent or patent application was specificallyand individually indicated to be incorporated by reference in itsentirety for all purposes.

The present invention can be implemented as a computer program productthat comprises a computer program mechanism embedded in a non-transitorycomputer readable storage medium. For instance, the computer programproduct could contain the program modules shown in any combination ofFIGS. 1, 2, and 3 and/or described in FIG. 4 or 5 . These programmodules can be stored on a CD-ROM, DVD, magnetic disk storage product,USB key, or any other non-transitory computer readable data or programstorage product.

Many modifications and variations of this invention can be made withoutdeparting from its spirit and scope, as will be apparent to thoseskilled in the art. The specific embodiments described herein areoffered by way of example only. The embodiments were chosen anddescribed in order to best explain the principles of the invention andits practical applications, to thereby enable others skilled in the artto best utilize the invention and various embodiments with variousmodifications as are suited to the particular use contemplated. Theinvention is to be limited only by the terms of the appended claims,along with the full scope of equivalents to which such claims areentitled.

1-20. (canceled)
 21. A method for treating erectile dysfunction in asubject, the method comprising: a) receiving a request for acGMP-specific phosphodiesterase 5 (PDE5) inhibitor pharmaceuticalcomposition; b) obtaining information, about the subject, theinformation comprising: a gender of the subject, an age of the subject,an erectile dysfunction status of the subject, whether the subject istaking a vasodilator composition comprising a nitrate or a nitrite,whether the subject is taking a guanylate cyclase stimulator medication,whether the subject is taking a PDE5 inhibitor pharmaceuticalcomposition, whether the subject has ever had a heart problem, a bloodpressure status of the subject, whether the subject has ever had astroke, whether the subject has a liver problem, a kidney functionstatus of the subject, whether the subject has retinitis pigmentosa,whether the subject has experienced vision loss, whether the subject hasever had a stomach ulcer, whether the subject has a bleeding disorder, agenital status of the subject, whether the subject has ever experiencedpriapism, whether the subject has a blood cell disorder, and whether thesubject is taking a medication that interacts with the PDE5 inhibitorpharmaceutical composition. c) comparing all or a portion of theinformation about the subject against a plurality of filters, wherein,when a respective filter in the plurality of filters is fired by thecomparing, the method is terminated or the subject is provided with awarning corresponding to the respective filter, and wherein theplurality of filters comprises: a gender filter that is fired when theinformation indicates that the subject is female, an age filter, anerectile dysfunction filter that is fired at least when the informationindicates that the subject does not have erectile dysfunction, avasodilator filter that is fired at least when the information indicatesthat the subject is taking a vasodilator composition comprising anitrate or a nitrite, a PDE5 inhibitor filter that is fired at leastwhen the information indicates that the subject is taking a PDE5inhibitor pharmaceutical composition, a guanylate cyclase stimulatorfilter that is fired at least when the information indicates that thesubject is taking a guanylate cyclase stimulator mediation, a heartproblem filter that is fired at least when the information indicatesthat the subject has had a heart problem, a blood pressure filter thatthis fired at least when the information indicates that the subject haseither (i) low blood pressure, or (ii) uncontrolled high blood pressure,a stroke filter that is fired at least when the information indicatesthat the subject has had a stroke, a liver disease filter that is firedat least when the information indicates that the subject has a liverproblem, a kidney disease filter that is fired at least when theinformation indicates that the subject has a kidney problem, a retinitispigmentosa filter that is fired at least when the information indicatesthat the subject has retinitis pigmentosa, a vision deterioration filterthat is fired at least when the information indicates that the subjecthas had severe vision loss, a stomach ulcer filter that is fired atleast when the information indicates that the subject has had a stomachulcer, a bleeding problem filter that is fired at least when theinformation indicates that the subject has a bleeding disorder, agenital abnormality filter that is fired at least when the informationindicates that the subject has an abnormal penile shape, a priapismfilter that is fired at least when the information indicates that thesubject has experienced priapism, a blood cell disorder filter that isfired at least when the information indicates that the subject has ablood cell disorder selected from the group consisting of sickle cellanemia, multiple myeloma, and leukemia, and a drug interaction filterthat is fired at least when the information indicates that the subjectis taking a medication that interacts with the PDE5 inhibitorpharmaceutical composition; and d) proceeding with the method, when themethod is not already terminated by the comparing, by authorizing aprovision of the PDE5 inhibitor pharmaceutical composition to thesubject; and e) administering the PDE5 inhibitor pharmaceuticalcomposition to the subject, after provision of the PDE5 inhibitorpharmaceutical composition has been authorized for the subject.
 22. Themethod of claim 21, the method further comprising receiving from thesubject an acknowledgement of each warning associated with each filterthat was fired in the comparing c) that did not terminate the method.23. The method of claim 21, the method further comprising communicatingan over-the-counter facts label for the PDE5 inhibitor pharmaceuticalcomposition to the subject before the authorization of the provision.24. The method of claim 23, the method further comprising receiving aconfirmation from the subject that the subject has received and read theover-the-counter facts label for the PDE5 inhibitor pharmaceuticalcomposition before the authorization of the provision.
 25. The method ofclaim 21, wherein the PDE5 inhibitor pharmaceutical composition has thestructure:

wherein: R⁰ represents hydrogen, halogen or C₁₋₆ alkyl; R¹ representshydrogen, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, haloC₁₋₆ alkyl, C₃₋₈cycloalkyl, C₃₋₈ cycloalkyl-C₁₋₃ alkyl, arylC₁₋₃ alkyl or heteroarylC₁₋₃alkyl; R² represents an optionally substituted mono-cyclic aromatic ringselected from benzene, thiophene, furan and pyridine or an optionallysubstituted bicyclic ring

 attached to the rest of the molecule via one of the benzene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which maybe saturated or partially or fully unsaturated and comprises carbonatoms and optionally one or two heteroatoms selected from oxygen,sulphur and nitrogen; and R³ represents hydrogen or C1-3 alkyl, or R¹and R³ together represent a 3- or 4-membered alkyl or alkenyl chain, ora pharmaceutically acceptable salt thereof.
 26. The method of claim 21,wherein the PDE5 inhibitor pharmaceutical composition is tadalafil or apharmaceutically acceptable salt thereof.
 27. The method of claim 23,the method further comprising receiving a confirmation from the subjectthat the over-the-counter drug facts label has been received and read,and wherein the subject is authorized for provision of a dosage of from2.5 mg to 10 mg of tadalafil no more than once per day.
 28. The methodof claim 23, the method further comprising receiving a confirmation fromthe subject that the over-the-counter drug facts label has been receivedand read, and wherein the subject is authorized for provision of adosage of 5 mg of tadalafil no more than once per day.
 29. The method ofclaim 21, wherein the PDE5 inhibitor pharmaceutical composition isvardenafil.
 30. The method of claim 21, wherein the age filter is firedwhen the information from the subject indicates that the subject is lessthan eighteen years old.
 31. The method of claim 21, wherein thevasodilator composition, which is capable of firing the vasodilatorfilter, includes a compound selected from the group consisting ofnitroglycerin, amyl nitrate, amyl nitrite, and butyl nitrate.
 32. Themethod of claim 21, wherein the drug interaction filter is fired whenthe first plurality of survey results indicates that the subject istaking a medication selected from the group consisting of an alphablocker, an HIV protease inhibitor, an antifungal medication, anantibiotic, a blood pressure medication, and an erectile dysfunctionmedication.
 33. The method of claim 21, wherein the heart problem, whichis capable of firing the heart problem filter, is selected from thegroup consisting of a heart attack, arrhythmia, angina, chest pain,narrowing of the aortic valve, and heart failure.
 34. The method ofclaim 21, wherein: the warning corresponding to a respective filter inthe plurality of filters that does not terminate the method comprises aprompt for the subject to indicate whether they have discussed the riskfactor underlying the respective filter in the plurality of filters thatwas fired with a health care provider; and acknowledgement is obtainedfrom the subject when the subject indicates that they have discussed therisk factor underlying the respective filter in the plurality of filtersthat was fired with a health care provider.
 35. The method of claim 21,further comprising storing a destination associated with the subject ina subject profile upon authorizing the provision.
 36. The method ofclaim 21, further comprising coordinating shipping of the PDE5 inhibitorpharmaceutical composition to a physical address associated with thesubject upon authorizing the provision.
 37. A method for treatingerectile dysfunction in a subject, the method comprising: a) receiving are-order request for a cGMP-specific phosphodiesterase 5 (PDE5)inhibitor pharmaceutical composition; b) obtaining information about thesubject, the information comprising: an erectile dysfunction status ofthe subject, whether the subject has started to take a vasodilatorcomposition comprising a nitrate or a nitrite since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, whether thesubject has started to take a guanylate cyclase stimulator medicationsince receiving their last provision of the PDE5 inhibitorpharmaceutical composition, whether the subject has started to take aPDE5 inhibitor pharmaceutical composition since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, whether thesubject has experienced a symptom of heart problems during sexualintercourse since receiving their last provision of the PDE5 inhibitorpharmaceutical composition, whether the subject has experienced priapismsince receiving their last provision of the PDE5 inhibitorpharmaceutical composition, whether the subject has experienced hearingor vision loss since receiving their last provision of the PDE5inhibitor pharmaceutical composition, whether the subject has developeda symptom of heart problems since receiving their last provision of thePDE5 inhibitor pharmaceutical composition, a blood pressure status ofthe subject, whether the subject has had a stroke since receiving theirlast provision of the PDE5 inhibitor pharmaceutical composition, whetherthe subject has developed a liver problem since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, a kidneyfunction status of the subject, whether the subject has developedretinitis pigmentosa since receiving their last provision of the PDE5inhibitor pharmaceutical composition, whether the subject has developeda stomach ulcer since receiving their last provision of the PDE5inhibitor pharmaceutical composition, whether the subject has developeda bleeding disorder since receiving their last provision of the PDE5inhibitor pharmaceutical composition, whether the subject has developedan abnormal genital shape since receiving their last provision of thePDE5 inhibitor pharmaceutical composition, whether the subject hasdeveloped a blood cell disorder since receiving their last provision ofthe PDE5 inhibitor pharmaceutical composition, and whether the subjecthas started taking a medication that interacts with the PDE5 inhibitorpharmaceutical composition since receiving their last provision of thePDE5 inhibitor pharmaceutical composition; c) comparing all or a portionof the information about the subject against a plurality ofre-assessment filters, wherein, when a respective re-assessment filterin the plurality of re-assessment filters is fired by the comparing, themethod is terminated or the subject is provided with a warningcorresponding to the respective re-assessment filter, and wherein theplurality of filters comprises: an erectile dysfunction re-assessmentfilter that is fired at least when the information indicates that thesubject does not have erectile dysfunction, a vasodilator re-assessmentfilter that is fired at least when the information indicates that thesubject is taking a vasodilator composition comprising a nitrate or anitrite, a guanylate cyclase stimulator re-assessment filter that isfired at least when the information indicates that the subject is takinga guanylate cyclase stimulator mediation, a PDE5 inhibitor re-assessmentfilter that is fired at least when the information indicates the subjectis taking a PDE5 inhibitor pharmaceutical composition; a sexualintercourse re-assessment filter that is fired at least when theinformation indicates that the subject has experienced a symptom ofheart problems during sexual intercourse since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, a priapismre-assessment filter that is fired at least when the informationindicates that the subject has had priapism since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, and asensory deterioration re-assessment filter that is fired at least whenthe information indicates that the subject has experienced a suddenvision loss or sudden hearing loss since receiving their last provisionof the PDE5 inhibitor pharmaceutical composition, a heart problemre-assessment filter that is fired at least when the informationindicates that the subject has developed a heart problem since receivingtheir last provision of the PDE5 inhibitor pharmaceutical composition, ablood pressure re-assessment filter that this fired at least when theinformation indicates that the subject has developed either (i) lowblood pressure, or (ii) uncontrolled high blood pressure, a strokere-assessment filter that is fired at least when the informationindicates that the subject has had a stroke since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, a liverdisease re-assessment filter that is fired at least when the informationindicates that the subject has developed liver disease since receivingtheir last provision of the PDE5 inhibitor pharmaceutical composition, akidney disease re-assessment filter that is fired at least when theinformation indicates that the subject has developed a kidney problemsince receiving their last provision of the PDE5 inhibitorpharmaceutical composition, a retinitis pigmentosa re-assessment filterthat is fired at least when the information indicates that the subjecthas been diagnosed with retinitis pigmentosa since receiving their lastprovision of the PDE5 inhibitor pharmaceutical composition, a stomachulcer re-assessment filter that is fired at least when the informationindicates that the subject has developed a stomach ulcer since receivingtheir last provision of the PDE5 inhibitor pharmaceutical composition, ableeding problem re-assessment filter that is fired at least when theinformation indicates that the subject has developed a bleeding disordersince receiving their last provision of PDE5 inhibitor pharmaceuticalcomposition, a genital abnormality re-assessment filter that is fired atleast when the information indicates that the subject has developed anabnormal genital shape since receiving their last provision of the PDE5inhibitor pharmaceutical composition, a blood cell disorderre-assessment filter that is fired at least when the informationindicates that the subject has developed a blood disorder selected fromthe group consisting of sickle cell anemia, multiple myeloma, andleukemia, since receiving their last provision of the PDE5 inhibitorpharmaceutical composition, and a drug interaction re-assessment filterthat is fired at least when the information indicates that the subjecthas started taking a medication that interacts with the PDE5 inhibitorpharmaceutical composition since receiving their last provision of thePDE5 inhibitor pharmaceutical composition; d) proceeding with the methodwhen the method is not already terminated by comparing c), byauthorizing a re-order provision of the PDE5 inhibitor pharmaceuticalcomposition to the subject; and (e) administering the PDE5 inhibitorpharmaceutical composition to the subject, following authorization ofthe re-order provision, to treat erectile dysfunction in the subject.38. The method of claim 37, the method further comprising receiving fromthe subject an acknowledgement of each warning associated with eachfilter that was fired in the comparing c) that does not terminate themethod.
 39. The method of claim 37, the method further comprisingcommunication an over-the-counter facts label for the PDE5 inhibitorpharmaceutical composition to the subject before the authorization ofthe re-order provision.
 40. The method of claim 39, the method furthercomprising receiving a confirmation from the subject that the subjecthas received and read the over-the-counter facts label for the PDE5inhibitor pharmaceutical composition before the authorization of there-order provision.
 41. The method of claim 37, wherein: the informationfurther comprises whether the subject has experienced a side effectassociated with the PDE5 inhibitor pharmaceutical composition sincereceiving their last provision of the PDE5 inhibitor pharmaceuticalcomposition, and the plurality of re-assessment filters furthercomprises a side effect re-assessment filter that is fired at least whenthe information indicates that the subject has experienced, sincereceiving their last provision of the PDE5 inhibitor pharmaceuticalcomposition, a side effect selected from the group consisting ofheadaches, abnormal vision, muscle pain, nausea, dizziness, and a skinrash.
 42. The method of claim 41, wherein the re-fulfillment methodfurther comprises, when a respective re-assessment filter in theplurality of re-assessment filters is fired, storing a record associatedwith the firing of the respective re-assessment filter in an adverseevent profile comprising records of re-assessment filter firing eventsassociated with a plurality of subjects.
 43. The method of claim 21,wherein at least one filter in the plurality of filters terminates themethod when fired and at least one filter in the plurality of filtersissues a warning when filed.
 44. The method of claim 37, wherein atleast one re-assessment filter in the plurality of re-assessment filtersterminates the method when fired and at least one re-assessment filterin the plurality of re-assessment filters issues a warning when filed.